Details of the Researcher

PHOTO

Taro Ozaki
Section
Graduate School of Pharmaceutical Sciences
Job title
Associate Professor
Degree
  • 博士(農学)(東京大学)

  • 修士(農学)(東京大学)

e-Rad No.
40709060
Researcher ID

Research History 4

  • 2021/09 - Present
    Tohoku University Graduate School of Pharmaceutical Sciences

  • 2016/04 - 2021/08
    Hokkaido University Faculty of Science Department of Chemistry Assistant Progessor

  • 2013/04 - 2016/03
    The University of Tokyo

  • 2010/04 - 2013/03
    日本学術振興会 特別研究員(DC1)

Education 2

  • 東京大学大学院 農学生命科学研究科 応用生命工学専攻

    2008/04 - 2013/03

  • The University of Tokyo

    2004/04 - 2008/03

Professional Memberships 5

  • 日本生薬学会

    2023/07 -

  • 日本薬学会

  • THE CHEMICAL SOCIETY OF JAPAN

  • SOCIETY OF ACTINOMYCETES JAPAN

  • JAPAN SOCIETY FOR BIOSICENCE, BIOTECHNOLOGY, AND AGROCHEMISTRY

Research Interests 5

  • 天然物化学

  • 糸状菌

  • 放線菌

  • 生合成

  • 抗生物質

Research Areas 1

  • Life sciences / Bioorganic chemistry /

Awards 3

  1. The Excellent Paper Award Published in Bioscience, Biotechnology, & Biochemistry

    2023/03 Structure and biosynthesis of the ribosomal lipopeptide antibiotic albopeptins

  2. 農芸化学奨励賞

    2022/03 公益社団法人 日本農芸化学会 酸化酵素を中心とした生物活性天然物の構造多様性創出機構に関する研究

  3. The Excellent Paper Award Published in Bioscience, Biotechnology, & Biochemistry

    2020/03 Biosynthetic study of conidiation-inducing factor conidiogenone: heterologous production and cyclization mechanism of a key bifunctional diterpene synthase

Papers 65

  1. Ketosynthase Domain Catalyzes β-Lactonization in the Biosynthesis of the HMG-CoA Synthase Inhibitor Hymeglusin. International-journal Peer-reviewed

    Mizuki Hirokawa, Taro Ozaki, Kento Tsukada, Akihiro Sugawara, Yohei Morishita, Teigo Asai

    Journal of the American Chemical Society 2025/07/10

    DOI: 10.1021/jacs.5c07060  

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    Hymeglusin (1) is a fungal polyketide consisting of a β-lactone ring with a unique (3R,4R) configuration. 1 is a potent 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) synthase inhibitor. Because it circumvents drug resistance in methicillin-resistant Staphylococcus aureus (MRSA), combination therapy using 1 would be a promising strategy for the treatment of infectious diseases caused by MRSA. Despite its pharmaceutical importance, the biosynthesis of 1, with respect to the formation of the characteristic β-lactone ring that is essential for its activity, had not been elucidated to date. During our genome mining of fungal highly reducing polyketide synthases (HR-PKSs), we identified a biosynthetic gene cluster for 1 in Nigrospora fungi. Heterologous expression and biochemical analysis of recombinant HR-PKS revealed that the ketosynthase (KS) domain of HR-PKS catalyzes the β-lactonization of the mature polyketide chain in the termination step. This study unveiled the previously unknown programming of HR-PKS catalysis and added one unique example to the noncanonical function of KS domains in type I PKS systems.

  2. Biosynthesis of Circumdatins Employs an Anthranilate Tailoring Pathway for NRPS Substrate Supplies Peer-reviewed

    Yura Sato, Yohei Morishita, Yuto Homma, Akihiro Sugawara, Ashaimaa Y. Moussa, Ahmed M. Elissawy, Abdel Nasser B. Singab, Taro Ozaki, Teigo Asai

    Organic Letters 2025/07/04

    DOI: 10.1021/acs.orglett.5c02131  

  3. Discovery and Theoretical Studies of Nonenzymatic Polyketide Dimerizations of Chaetophenols Peer-reviewed

    Hiroto Matsui, Yohei Morishita, Takashi Yamamoto, Taro Ozaki, Akihiro Sugawara, Yui Masumoto, Mamoru Watanabe, Ayumi Watanabe, Hajime Sato, Junichiro Kanazawa, Tohru Taniguchi, Masanobu Uchiyama, Teigo Asai

    Organic Letters 2025/02/07

    DOI: 10.1021/acs.orglett.4c04346  

  4. Semi-synthesis of a DNA-Tagged Polyketide–Peptide Hybrid Macrocycle Using a Biosynthetically Prepared Fungal Macrolide as a Synthetic Component Peer-reviewed

    Soya Koremura, Akihiro Sugawara, Yohei Morishita, Taro Ozaki, Teigo Asai

    Organic Letters 2024/10/25

    DOI: 10.1021/acs.orglett.4c03588  

  5. In vivo and in vitro reconstitution of biosynthesis of N-prenylated phenazines revealing diverse phenazine-modifying enzymes. International-journal Peer-reviewed

    Teruhito Kato, Dan Xia, Taro Ozaki, Tomoyo Nakao, Ping Zhao, Makoto Nishiyama, Taro Shiraishi, Tomohisa Kuzuyama

    Chembiochem : a European journal of chemical biology e202400723 2024/10/16

    DOI: 10.1002/cbic.202400723  

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    Phenazine natural products play various roles such as signal molecules, antibiotics, or electron carriers in their producer strains. Among these products, phenazinomycin and lavanducyanin, which are produced by Streptomyces species, are characterized by an N-alkyl modification. Herein, we established the biosynthetic pathways for these two phenazine natural products. Gene-disruption experiments and in vitro reconstitution of the phenazine-tailoring pathway revealed the late steps of the biosynthetic pathway of the phenazines. The class II terpene cyclase homolog Pzm1 catalyzes the cyclization reaction of farnesyl diphosphate to form monocyclic farnesyl diphosphate. Additionally, the prenyltransferase homolog PzmP functions as the N-prenyltransferase of 5,10-dihydrophenazine-1-carboxylic acid. The flavin monooxygenase homolog PzmS catalyzes the oxidative decarboxylation of prenylated 5,10-dihydrophenazine-1-carboxylic acid to yield phenazinomycin. This study highlights unprecedented modification enzymes for phenazine natural products.

  6. Subcellular compartmentalized localization of transmembrane proteins essential for production of fungal cyclic peptide cyclochlorotine. International-journal Peer-reviewed

    Takuya Katayama, Yulu Jiang, Taro Ozaki, Hideaki Oikawa, Atsushi Minami, Jun-Ichi Maruyama

    Bioscience, biotechnology, and biochemistry 2024/09/04

    DOI: 10.1093/bbb/zbae122  

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    Fungal biosynthetic gene clusters often include genes encoding transmembrane proteins, which have been mostly thought to be transporters exporting the products. However, there is little knowledge about subcellular compartmentalization of transmembrane proteins essential for biosynthesis. Fungal mycotoxin cyclochlorotine is synthesized by non-ribosomal peptide synthetase, which is followed by modifications with three transmembrane UstYa-family proteins. Heterologous expression in Aspergillus oryzae revealed that total biosynthesis of cyclochlorotine requires additional two transporter proteins. Here, we investigated subcellular localizations of the five transmembrane proteins under heterologous expression in A. oryzae. Enhanced green fluorescent protein (EGFP) fusions to the transmembrane proteins, which were confirmed to normally function in cyclochlorotine production, were expressed together with organellar markers. All the transmembrane proteins exhibited localizations commonly in line of the trans-Golgi, endosomes, and vacuoles. This study suggests that subcellular compartmentalization of UstYa family proteins and transporters allows corporative functions of delivering intermediates and subsequent modifications, completing cyclochlorotine biosynthesis.

  7. Bioinformatics-Guided Reconstitution of Biosynthetic Machineries of Fungal Eremophilane Sesquiterpenes Peer-reviewed

    Yoshiro Sato, Xinge Shi, Ying Ye, Saori Domon, Junya Takino, Taro Ozaki, Chengwei Liu, Hideaki Oikawa, Atsushi Minami

    ACS Chemical Biology 2024/04/19

    DOI: 10.1021/acschembio.4c00040  

  8. Genome mining of labdane-related diterpenoids: Discovery of the two-enzyme pathway leading to (−)-sandaracopimaradiene in the fungus Arthrinium sacchari Invited Peer-reviewed

    Fumito Sato, Terutaka Sonohara, Shunta Fujiki, Akihiro Sugawara, Yohei Morishita, Taro Ozaki, Teigo Asai

    Beilstein Journal of Organic Chemistry 2024/04/03

    DOI: 10.3762/bjoc.20.65  

  9. A new 3,6-dialkyl-α-pyrone produced by the heterologous expression of a PKS-NRPS hybrid enzyme derived from a Pestalotiopsis endophyte Peer-reviewed

    Yue Shi, Taro Ozaki, Akihiro Sugawara, Yohei Morishita, Yu Pei Tan, Roger G. Shivas, Rohan A. Davis, Teigo Asai

    Tetrahedron Letters 2024/01

    DOI: 10.1016/j.tetlet.2023.154865  

  10. Total Biosynthesis of Melleolides from Basidiomycota Fungi: Mechanistic Analysis of the Multi-Functional GMC Oxidase Mld7. International-journal Peer-reviewed

    Mitsunori Fukaya, Shota Nagamine, Taro Ozaki, Yaping Liu, Miina Ozeki, Taro Matsuyama, Kazunori Miyamoto, Hirokazu Kawagishi, Masanobu Uchiyama, Hideaki Oikawa, Atsushi Minami

    Angewandte Chemie (International ed. in English) e202308881 2023/08/03

    DOI: 10.1002/anie.202308881  

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    Mushroom terpenoids are biologically and chemically diverse fungal metabolites. Among them, melleolides are representative sesquiterpenoids with a characteristic protoilludane skeleton. In this study, we applied a recently established hot spot knock-in method to elucidate the biosynthetic pathway leading to 1a-hydroxymelleolide. The biosynthesis of the sesquiterpene core involves the cytochrome P450 catalyzing stepwise hydroxylation on the D6-protoilludene framework and a stereochemical inversion process at the C5 position catalyzed by short-chain dehydrogenase/reductase family proteins. The highlight on the biosynthesis is that the flavoprotein Mld7 catalyzes an oxidation triggered double bond shift accompanying dehydration and acyl group assisted substitution with two different nucleophiles at the C6 position to afford the D7-protoilludene derivatives such as melleolide and armillarivin. The complex reaction mechanism was proposed by density functional theory (DFT) calculations. Of particularly importance is that product distribution is regulated by the interaction with cell membrane. This proposed biosynthetic pathway provides an opportunity to understand the structural diversification mechanisms of melleolides and protoilludane sesquiterpenes.

  11. Structural diversification of fungal natural products by oxidative enzymes. International-journal Invited Peer-reviewed

    Taro Ozaki

    Bioscience, biotechnology, and biochemistry 87 (8) 809-818 2023/07/24

    DOI: 10.1093/bbb/zbad062  

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    Ascomycota and basidiomycota fungi are prolific producers of biologically active natural products. Fungal natural products exhibit remarkable structural diversity and complexity, which are generated by the enzymes involved in their biosynthesis. After the formation of core skeletons, oxidative enzymes play a critical role in converting them into mature natural products. Besides simple oxidations, more complex transformations, such as multiple oxidations by single enzymes, oxidative cyclization, and skeletal rearrangement, are often observed. Those oxidative enzymes are of significant interest for the identification of new enzyme chemistry and have the potential to be biocatalysts for the synthesis of complex molecules. This review presents selected examples of unique oxidative transformations that have been found in the biosynthesis of fungal natural products. The development of strategies for refactoring the fungal biosynthetic pathways with an efficient genome-editing method is also introduced.

  12. Oxidative bicyclic ring system formation involving indole diterpene biosynthesis: Remarkable substrate tolerance of a prenyltransferase and flavoprotein oxidase Peer-reviewed

    Yaping Liu, Taro Ozaki, Atsushi Minami, Hideaki Oikawa

    Tetrahedron Letters 2023/03

    DOI: 10.1016/j.tetlet.2023.154374  

  13. Identification and Functional Characterization of Fungal Chalcone Synthase and Chalcone Isomerase International-journal Peer-reviewed

    Sho Furumura, Taro Ozaki, Akihiro Sugawara, Yohei Morishita, Kento Tsukada, Tatsuya Ikuta, Asuka Inoue, Teigo Asai

    Journal of Natural Products 86 (2) 398-405 2023/02/10

    DOI: 10.1021/acs.jnatprod.2c01027  

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    By mining fungal genomic information, a noncanonical iterative type I PKS fused with an N-terminal adenylation-thiolation didomain, which catalyzes the formation of naringenin chalcone, was found. Structural prediction and molecular docking analysis indicated that a C-terminal thioesterase domain was involved in the Claisen-type cyclization. An enzyme responsible for formation of (2S)-flavanone in the biosynthesis of fungal flavonoids was also identified. Collectively, these findings demonstrate unprecedented fungal biosynthetic machinery leading to plant-like metabolites.

  14. Recent advances in the biosynthesis of ribosomally synthesized and posttranslationally modified peptides of fungal origin. International-journal Peer-reviewed

    Taro Ozaki, Atsushi Minami, Hideaki Oikawa

    The Journal of antibiotics 2022/11/24

    DOI: 10.1038/s41429-022-00576-w  

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    Ribosomally synthesized and posttranslationally modified peptides (RiPPs) are growing class of natural products with potent biological activities. Although the core scaffolds of RiPPs are composed of proteinogenic amino acids, remarkable structural diversity is generated through posttranslational modifications (PTMs) of precursor peptides. In addition, ribosomal origin of biosynthetic precursors enables supply of its analogs through genetic approach such as site-directed mutagenesis on corresponding genes. As PTM enzymes often exhibit substrate tolerance, RiPP biosynthetic machineries are considered as efficient tools for generation of unique peptide derivatives. RiPP pathways are distributed among all domains of life and those derived from bacteria and plants have been known for decades. In contrast, fungal RiPPs (F-RiPPs) have fewer examples. Amatoxins and omphalotins are F-RiPPs produced by Basidiomycota fungi. In the biosynthesis of these compounds, macrocyclization by prolyl oligopeptidase homologs and N-methylations of back bone amides have been characterized, respectively. Ustiloxins and related compounds are another group of F-RiPPs with characteristic macrocyclic ethers. UstYa family proteins, which are fungi-specific putative oxidases, have been identified as common proteins involved in PTMs of these compounds. Despite a limited number of characterized examples, recent progress in sequencing of fungal genomes indicated that a number of RiPP pathways are hidden in fungal resources, making F-RiPPs as attractive target for genome mining studies while more detailed understandings of key biosynthetic enzymes are still necessary. This review seeks to describe recent advances on the F-RiPP biosynthesis with slight emphasis on the function of UstYa family proteins.

  15. Elucidation of Late-Stage Biosynthesis of Phomoidride: Proposal of Cyclization Mechanism Affording Characteristic Nine-Membered Ring of Fungal Dimeric Anhydride. International-journal Peer-reviewed

    Shintaro Yamamoto, Taro Matsuyama, Taro Ozaki, Junya Takino, Hajime Sato, Masanobu Uchiyama, Atsushi Minami, Hideaki Oikawa

    Journal of the American Chemical Society 144 (46) 20998-21004 2022/11/23

    DOI: 10.1021/jacs.2c09308  

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    Antihypercholesterolemic agent phomoidride (PMD) B has a highly elaborated bicyclo[4.3.1]deca-1,6-diene core scaffold derived from dimeric anhydride with a nine-membered ring. This report elucidated the late stage transformation from an anhydride monomer to PMD B through the heterologous expression of three enzyme genes, TstC, TstK, and TstE. Additional in vitro studies of TstK and TstE provided evidence on the formation of PMD via dimerization, three-step oxidation, and unusual methylation-triggered bicyclic ketal formation. Elucidation of the function of cyclase TstC prompts us to examine the cyclization mechanism of TstC by using a computational approach. Computational analytical data on PMD and structurally related glaucanic acid indicated that the initial decarboxylation of monomer results in enolate and subsequent double Michael reactions of another monomer, followed by an optional aldol reaction proceeding in an endo-selective manner to give cycloadducts, supporting the fact that the starting orientation of two monomers is directly transferred to the product configurations.

  16. Biosynthesis of indole diterpenes: a reconstitution approach in a heterologous host. International-journal Peer-reviewed

    Taro Ozaki, Atsushi Minami, Hideaki Oikawa

    Natural product reports 2022/11/02

    DOI: 10.1039/d2np00031h  

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    Covering: 2013 to 2022In this review, we provide an overview elucidating the biosynthetic pathway and heterologous production of fungal indole diterpenes (IDTs). Based on the studies of six IDT biosynthesis, we extracted nature's strategy: (1) two-stage synthesis for the core scaffold and platform intermediates, and (2) late-stage modifications for installing an additional cyclic system on the indole ring. Herein, we describe reconstitution studies applying this strategy to the synthesis of highly elaborated IDTs. We also discuss its potential for future biosynthetic engineering.

  17. Structure and biosynthesis of the ribosomal lipopeptide antibiotic albopeptins. International-journal Peer-reviewed

    Hideaki Oikawa, Yusuke Mizunoue, Takemichi Nakamura, Eri Fukushi, Jiang Yulu, Taro Ozaki, Atsushi Minami

    Bioscience, biotechnology, and biochemistry 86 (6) 717-723 2022/05/24

    DOI: 10.1093/bbb/zbac039  

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    Albopeptins produced by Streptomyces albofaciens JC-82-120 were isolated as effective antibiotics for plant pathogenetic disease in 1986. However, their unusual physicochemical properties hampered the determination of their chemical structures. In this report, we describe our efforts to elucidate their structures. Initially, the structure of an unusual C15-fatty acid with an N-hydroxyguanidyl group was determined using degradation and chemical synthesis. After the linear portion of the octapeptide core was constructed based on the 2D-NMR data, the final assembly of the unusual structure, including the sulfoxide bridge, was achieved through the analysis of detailed NMR data. The proposed structure of albopeptin B was supported by MS/MS data, which also enabled us to determine the structure of five albopeptin family members. Bioinformatics analysis of the genomic data of the producer strain further led us to propose that their biosynthetic pathway is similar to the ribosomally derived lanthipeptides possessing a long-chain fatty acid.

  18. Discovery of a Cyclic Depsipeptide from Chaetomium mollipilium by the Genome Mining Approach. International-journal Peer-reviewed

    Yuto Homma, Akihiro Sugawara, Yohei Morishita, Kento Tsukada, Taro Ozaki, Teigo Asai

    Organic letters 24 (19) 3504-3509 2022/05/20

    DOI: 10.1021/acs.orglett.2c01172  

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    Genome mining and bioinformatics analyses allowed us to rationally find a candidate biosynthetic gene cluster for a new cyclic depsipeptide of Chaetomium mollipilium. A heterologous reconstitution of the identified biosynthetic pathway predictably afforded a new cyclic depsipeptide composed of l-leucine, l-tryptophan, and a polyketide moiety. Interestingly, the 10-membered macrocycle structure generated equilibrium to an unprecedented cyclol structure. This study demonstrates the advantage of a synthetic biology method in achieving rational access to new natural products.

  19. Biosynthetic machineries of anthraquinones and bisanthraquinones in Talaromyces islandicus. International-journal Peer-reviewed

    Mitsunori Fukaya, Taro Ozaki, Atsushi Minami, Hideaki Oikawa

    Bioscience, biotechnology, and biochemistry 86 (4) 435-443 2022/03/21

    DOI: 10.1093/bbb/zbac009  

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    Talaromyces islandicus is a unique fungus that produces more than 20 numbers of anthraquinones (AQs) and their dimeric natural products, bisanthraquinones (BQs). These compounds share a 9,10-anthracenedione core derived from emodin. The biosynthetic pathway of emodin has been firmly established, while that of other AQs and BQs is still unclear. In this study, we identified the biosynthetic gene clusters for chrysophanol and skyrin. The function of key modification enzymes was examined by performing biotransformation experiments and in vitro enzymatic reactions with emodin and its derivatives, allowing us to propose a mechanism for the modification reactions. The present study provides insight into the biosynthesis of AQs and BQs in T. islandicus.

  20. Heterologous expression of a polyketide synthase ACRTS2 in Aspregillus oryzae produces host selective ACR-toxins: Co-production of minor metabolites. International-journal Peer-reviewed

    Akari Kotani, Taro Ozaki, Junya Takino, Susumu Mochizuki, Kazuya Akimitsu, Atsushi Minami, Hideaki Oikawa

    Bioscience, biotechnology, and biochemistry 86 (3) 287-293 2021/12/11

    DOI: 10.1093/bbb/zbab214  

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    Previously, we succeeded to produce the core structure of the host-selective ACR-toxin (1) on brown leaf spot on rough lemon when the polyketide synthase ACRTS2 gene was heterologously expressed in Aspergillus oryzae (AO). To confirm the production of 1 in AO, the detection limit and suppressing decarboxylation were improved, and these efforts led us to conclude the direct production of 1 instead of its decarboxylation product. During this examination, minor ACR-toxin-related metabolites were found. Their structure determination enabled us to propose a decarboxylation mechanism and novel branching route forming byproducts from the coupling of the dihydropyrone moiety of 1 with the acetaldehyde and kojic acid abundant in AO. The involvement of putative cyclase ACRTS3 in the chain release of linear polyketide was excluded by the co-expression analysis of ACRTS2 and ACRTS3. Taken together, we concluded the production of 1 in AO is solely responsible for ACRTS2.

  21. Biosynthetic Studies of Phomopsins Unveil Posttranslational Installation of Dehydroamino Acids by UstYa Family Proteins. International-journal Peer-reviewed

    Hideaki Oikawa, Kaho Sogahata, Taro Ozaki, Yuya Igarashi, Yuka Naganuma, Chengwei Liu, Atsushi Minami

    Angewandte Chemie (International ed. in English) 2021/10/04

    DOI: 10.1002/anie.202111076  

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    UstYa family proteins (DUF3328) are widely and specifically distributed in fungi. They are known to be involved in the biosynthesis of ribosomally synthesized and posttranslationally modified peptides (RiPPs) and nonribosomal peptides, and possibly catalyze various reactions, including oxidative cyclization and chlorination. In this study, we focused on phomopsin A, a fungal RiPP consisting of unique nonproteinogenic amino acids. Gene knockout experiments demonstrated that three UstYa homologues, phomYc , phomYd , and phomYe , are essential for the desaturation of amino acid moieties, showing unprecedented function among UstYa family proteins. Sequence similarity network analysis indicated that their amino acid sequences are highly diverged, and that most remain uncharacterized, paving the way for genome mining of fungal metabolites with unique modifications.

  22. Biochemistry-Guided Prediction of the Absolute Configuration of Fungal Reduced Polyketides. International-journal Peer-reviewed

    Junya Takino, Akari Kotani, Taro Ozaki, Wenquan Peng, Jie Yu, Yian Guo, Susumu Mochizuki, Kazuya Akimitsu, Masaru Hashimoto, Tao Ye, Atsushi Minami, Hideaki Oikawa

    Angewandte Chemie (International ed. in English) 60 (43) 23403-23411 2021/08/26

    DOI: 10.1002/anie.202110658  

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    Highly reducing polyketide synthases (HR-PKSs) produce structurally diverse polyketides (PKs). The PK diversity is constructed by a variety of factors, including the β-keto processing, chain length, methylation pattern, and relative and absolute configurations of the substituents. We examined the stereochemical course of the PK processing for the synthesis of polyhydroxy PKs such as phialotides, phomenoic acid, and ACR-toxin. Heterologous expression of a HR-PKS gene, a trans-acting enoylreductase gene, and a truncated non-ribosomal peptide synthetase gene resulted in the formation of a linear PK with multiple stereogenic centers. The absolute configurations of the stereogenic centers were determined by chemical degradation followed by comparison of the degradation products with synthetic standards. A stereochemical rule was proposed to explain the absolute configurations of other reduced PKs and highlights an error in the absolute configurations of a reported structure. The present work demonstrates that focused functional analysis of functionally related HR-PKSs leads to a better understanding of the stereochemical course.

  23. Genome-Based Discovery of Enantiomeric Pentacyclic Sesterterpenes Catalyzed by Fungal Bifunctional Terpene Synthases. International-journal Peer-reviewed

    Lan Jiang, Xue Zhang, Yuya Sato, Guoliang Zhu, Atsushi Minami, Weiyan Zhang, Taro Ozaki, Bin Zhu, Zhixin Wang, Xinye Wang, Kangjie Lv, Jingyu Zhang, Yongheng Wang, Shushan Gao, Chengwei Liu, Tom Hsiang, Lixin Zhang, Hideaki Oikawa, Xueting Liu

    Organic letters 23 (12) 4645-4650 2021/06/18

    DOI: 10.1021/acs.orglett.1c01361  

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    Genome-based discovery of two previously unreported fungal bifunctional terpene synthases (BFTSs) from phytopathogenic fungi are reported: FoFS catalyzing the formation of fusoxypenes A-C (1-3) and (-)-astellatene (4) and AtAS capable of synthesizing preaspterpenacid I (6). Interestingly, FoFS and AtAS catalyzed the formation of enantiomeric sesterterpenes with a 5-6-7-3-5 ring system. C22-oxidative modification of preaspterpenacid I by AtP450 was characterized as well. Plausible cyclization pathways of the fusoxypenes were illustrated by DFT calculations.

  24. Biosynthesis of Cyclochlorotine: Identification of the Genes Involved in Oxidative Transformations and Intramolecular O,N-Transacylation. International-journal Peer-reviewed

    Yulu Jiang, Taro Ozaki, Chengwei Liu, Yuya Igarashi, Ying Ye, Shoubin Tang, Tao Ye, Jun-Ichi Maruyama, Atsushi Minami, Hideaki Oikawa

    Organic letters 23 (7) 2616-2620 2021/04/02

    DOI: 10.1021/acs.orglett.1c00525  

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    Mycotoxin cyclochlorotine (1) and structurally related astins are cyclic pentapeptides containing unique nonproteinogenic amino acids, such as β-phenylalanine, l-allo-threonine, and 3,4-dichloroproline. Herein, we report the biosynthetic pathway for 1, which involves intriguing tailoring processes mediated by DUF3328 proteins, including stereo- and regiospecific chlorination and hydroxylation and intramolecular O,N-transacylation. Our findings demonstrate that DUF3328 proteins, which are known to be involved in oxidative cyclization of fungal ribosomal peptides, have much higher functional diversity than previously expected.

  25. Acyltransferase that catalyses the condensation of polyketide and peptide moieties of goadvionin hybrid lipopeptides. International-journal Peer-reviewed

    Ryosuke Kozakai, Takuto Ono, Shotaro Hoshino, Hidenori Takahashi, Yohei Katsuyama, Yoshinori Sugai, Taro Ozaki, Kazuya Teramoto, Kanae Teramoto, Koichi Tanaka, Ikuro Abe, Shumpei Asamizu, Hiroyasu Onaka

    Nature chemistry 12 (9) 869-877 2020/09

    DOI: 10.1038/s41557-020-0508-2  

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    Fusions of fatty acids and peptides expand the structural diversity of natural products; however, polyketide/ribosomally synthesized and post-translationally modified peptides (PK/RiPPs) hybrid lipopeptides are relatively rare. Here we report a family of PK/RiPPs called goadvionins, which inhibit the growth of Gram-positive bacteria, and an acyltransferase, GdvG, which catalyses the condensation of the PK and RiPP moieties. Goadvionin comprises a trimethylammonio 32-carbon acyl chain and an eight-residue RiPP with an avionin structure. The positions of six hydroxyl groups and one double bond in the very-long acyl chain were determined by radical-induced dissociation tandem mass spectrometry, which collides radical ion species to generate C-C bond cleavage fragments. GdvG belongs to the Gcn5-related N-acetyltransferase superfamily. Unlike conventional acyltransferases, GdvG transfers a very long acyl chain that is tethered to an acyl carrier protein to the N-terminal amino group of the RiPP moiety. gdvG homologues flanked by PK/fatty acid and RiPP biosynthesis genes are widely distributed in microbial species, suggesting that acyltransferase-catalysed condensation of PKs and RiPPs is a general strategy in biosynthesis of similar lipopeptides.

  26. Predicting the chemical space of fungal polyketides by phylogeny-based bioinformatics analysis of polyketide synthase-nonribosomal peptide synthetase and its modification enzymes. International-journal Peer-reviewed

    Atsushi Minami, Takahiro Ugai, Taro Ozaki, Hideaki Oikawa

    Scientific reports 10 (1) 13556-13556 2020/08/11

    DOI: 10.1038/s41598-020-70177-w  

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    Fungal polyketide synthase (PKS)-nonribosomal peptide synthetase (NRPS) hybrids are key enzymes for synthesizing structurally diverse hybrid natural products (NPs) with characteristic biological activities. Predicting their chemical space is of particular importance in the field of natural product chemistry. However, the unexplored programming rule of the PKS module has prevented prediction of its chemical structure based on amino acid sequences. Here, we conducted a phylogenetic analysis of 884 PKS-NRPS hybrids and a modification enzyme analysis of the corresponding biosynthetic gene cluster, revealing a hidden relationship between its genealogy and core structures. This unexpected result allowed us to predict 18 biosynthetic gene cluster (BGC) groups producing known carbon skeletons (number of BGCs; 489) and 11 uncharacterized BGC groups (171). The limited number of carbon skeletons suggests that fungi tend to select PK skeletons for survival during their evolution. The possible involvement of a horizontal gene transfer event leading to the diverse distribution of PKS-NRPS genes among fungal species is also proposed. This study provides insight into the chemical space of fungal PKs and the distribution of their biosynthetic gene clusters.

  27. Biosynthesis of Indole Diterpene Lolitrems: Radical-Induced Cyclization of an Epoxyalcohol Affording a Characteristic Lolitremane Skeleton. International-journal Peer-reviewed

    Yulu Jiang, Taro Ozaki, Mei Harada, Tadachika Miyasaka, Hajime Sato, Kazunori Miyamoto, Junichiro Kanazawa, Chengwei Liu, Jun-Ichi Maruyama, Masaatsu Adachi, Atsuo Nakazaki, Toshio Nishikawa, Masanobu Uchiyama, Atsushi Minami, Hideaki Oikawa

    Angewandte Chemie (International ed. in English) 59 (41) 17996-18002 2020/07/16

    DOI: 10.1002/anie.202007280  

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    Lolitrems are tremorgenic indole diterpenes that exhibit a unique 5/6 bicyclic system of the indole moiety. Although genetic analysis has indicated that the prenyltransferase LtmE and the cytochrome P450 LtmJ are involved in the construction of this unique structure, the detailed mechanism remains to be elucidated. Herein, we report the reconstitution of the biosynthetic pathway for lolitrems employing a recently established genome-editing technique for the expression host Aspergillus oryzae. Heterologous expression and bioconversion of the various intermediates revealed that LtmJ catalyzes multistep oxidation to furnish the lolitrem core. We also isolated the key reaction intermediate with an epoxyalcohol moiety. This observation allowed us to establish the mechanism of radical-induced cyclization, which was firmly supported by density functional theory calculations and a model experiment with a synthetic analogue.

  28. Minimal lactazole scaffold for in vitro thiopeptide bioengineering. International-journal Peer-reviewed

    Alexander A Vinogradov, Morito Shimomura, Yuki Goto, Taro Ozaki, Shumpei Asamizu, Yoshinori Sugai, Hiroaki Suga, Hiroyasu Onaka

    Nature communications 11 (1) 2272-2272 2020/05/08

    DOI: 10.1038/s41467-020-16145-4  

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    Lactazole A is a cryptic thiopeptide from Streptomyces lactacystinaeus, encoded by a compact 9.8 kb biosynthetic gene cluster. Here, we establish a platform for in vitro biosynthesis of lactazole A, referred to as the FIT-Laz system, via a combination of the flexible in vitro translation (FIT) system with recombinantly produced lactazole biosynthetic enzymes. Systematic dissection of lactazole biosynthesis reveals remarkable substrate tolerance of the biosynthetic enzymes and leads to the development of the minimal lactazole scaffold, a construct requiring only 6 post-translational modifications for macrocyclization. Efficient assembly of such minimal thiopeptides with FIT-Laz opens access to diverse lactazole analogs with 10 consecutive mutations, 14- to 62-membered macrocycles, and 18 amino acid-long tail regions, as well as to hybrid thiopeptides containing non-proteinogenic amino acids. This work suggests that the minimal lactazole scaffold is amenable to extensive bioengineering and opens possibilities to explore untapped chemical space of thiopeptides.

  29. Oxidative Ring Contraction by a Multifunctional Dioxygenase Generates the Core Cycloocatadiene in the Biosynthesis of Fungal Dimeric Anhydride Zopfiellin. International-journal Peer-reviewed

    Tetsuya Shiina, Taro Ozaki, Yusuke Matsu, Shota Nagamine, Chengwei Liu, Masaru Hashimoto, Atsushi Minami, Hideaki Oikawa

    Organic letters 22 (5) 1997-2001 2020/03/06

    DOI: 10.1021/acs.orglett.0c00340  

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    To elucidate the biosynthesis of a fungicidal dimeric anhydride zopfiellin, the putative biosynthetic gene cluster was identified. We conducted heterologous expression of candidate genes for the synthesis of maleic anhydride and its dimerization and identified the two isomeric dimers with 9-membered rings as products. Notably, α-ketoglutarate-dependent dioxygenase ZopK oxidized one of the dimers, giving the 8-membered ring of zopfiellin. The mechanism of oxidative rearrangement is proposed by analyzing the incorporation of 13C-labeled precursors.

  30. Efficient Reconstitution of Basidiomycota Diterpene Erinacine Gene Cluster in Ascomycota Host Aspergillus oryzae Based on Genomic DNA Sequences. International-journal Peer-reviewed

    Liu C, Minami A, Ozaki T, Wu J, Kawagishi H, Maruyama JI, Oikawa H

    Journal of the American Chemical Society 141 (39) 15519-15523 2019/10

    DOI: 10.1021/jacs.9b08935  

    ISSN: 0002-7863

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    To develop the versatile methodology for genome mining of mushroom metabolites, we examined the production of bioactive diterpenes erinacines using genomic DNA sequences. In this report, we initially identified high expression loci (hot spots) in Aspergillus oryzae by sequencing the genomic DNAs from highly yielding transformants which were obtained in our previous biosynthetic studies. Genome editing knock-in of all erinacine biosynthetic genes directly to the hot spot showed that A. oryzae correctly spliced more than 90% of the introns in the mushroom genomic DNA gene sequences. Then, we reconstituted the erinacine biosynthetic gene cluster using two rounds of knock-in of the cDNAs and newly developed repeatable genetic engineering by plasmid recycling. At 100% transformation rate, we obtained a transformant that successfully produced erinacine Q and its intermediates. In this study, we elucidated a biosynthetic pathway of erinacines involving functionally unique hydroxylation supported by dehydrogenase EriH and xylose-specific glycosylation by introducing plant genes for supplying UDP-xylose. Our newly developed hot spot knock-in and plasmid recycling allowed us to avoid a time-consuming screening process and to use unlimited introduction of biosynthetic genes due to marker-free genome editing.

  31. Chemical Interactions of Cryptic Actinomycete Metabolite 5‐Alkyl‐1,2,3,4‐tetrahydroquinolines through Aggregate Formation

    Ryosuke Sugiyama, Takahiro Nakatani, Shinichi Nishimura, Kei Takenaka, Taro Ozaki, Shumpei Asamizu, Hiroyasu Onaka, Hideaki Kakeya

    Angewandte Chemie 131 (38) 13620-13625 2019/09/16

    Publisher: Wiley

    DOI: 10.1002/ange.201905970  

  32. Elucidation of biosynthetic pathway of a plant hormone abscisic acid in phytopathogenic fungi Peer-reviewed

    Junya Takino, Takuto Kozaki, Taro Ozaki, Chengwei Liu, Atsushi Minami, Hideaki Oikawa

    Bioscience, Biotechnology, and Biochemistry 1-8 2019/09/02

    Publisher: Informa {UK} Limited

    DOI: 10.1080/09168451.2019.1618700  

    ISSN: 0916-8451

  33. Chemical Interactions of Cryptic Actinomycete Metabolite 5-Alkyl-1,2,3,4-tetrahydroquinolines through Aggregate Formation. International-journal Peer-reviewed

    Sugiyama R, Nakatani T, Nishimura S, Takenaka K, Ozaki T, Asamizu S, Onaka H, Kakeya H

    Angewandte Chemie (International ed. in English) 58 (38) 13486-13491 2019/09

    DOI: 10.1002/anie.201905970  

    ISSN: 1433-7851

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    Organisms often produce secondary metabolites as a mixture of biosynthetically related congeners. However, why are metabolites with minor chemical variations produced simultaneously? 5-Alkyl-1,2,3,4-tetrahydroquinolines (5aTHQs) are small, lipophilic metabolites produced by Streptomyces nigrescens HEK616 when cultured with Tsukamurella pulmonis TP-B0596. A mixture of 5aTHQs forms aggregates that show enhanced membrane affinity and biological activity. The ability to form aggregates and membrane-binding activity is regulated by the length of the alkyl chains. Aggregates with long alkyl chains were too stable to fuse with lipid membranes. However, if inactive 5aTHQ congener was mixed with active congener, the mixture showed increased membrane affinity, enabling cellular entry and biological activity. Therefore, it is shown that sloppiness in a biosynthetic pathway, by which minor structural variations can be produced, is functionally rational, as the metabolites show synergistic action.

  34. Biosynthetic machinery of 6-hydroxymellein derivatives leading to cyclohelminthols and palmaenones. Peer-reviewed

    Ugai T, Minami A, Tanaka S, Ozaki T, Liu C, Shigemori H, Hashimoto M, Oikawa H

    Chembiochem : a European journal of chemical biology 2019/07

    DOI: 10.1002/cbic.201900404  

    ISSN: 1439-4227

  35. Ascomycota Aspergillus oryzae is an efficient expression host for production of Basidiomycota terpenes using genomic DNA sequences. International-journal Peer-reviewed

    Nagamine S, Liu C, Nishishita J, Kozaki T, Sogahata K, Sato Y, Minami A, Ozaki T, Schmidt-Dannert C, Maruyama JI, Oikawa H

    Applied and environmental microbiology 85 (15) 2019/05

    DOI: 10.1128/AEM.00409-19  

    ISSN: 0099-2240

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    Basidiomycete fungi are an attractive resource for biologically active natural products for use in pharmaceutically relevant compounds. Recently, genome projects on mushroom fungi have provided a great deal of biosynthetic gene cluster information. However, functional analyses of the gene clusters for natural products were largely unexplored because of the difficulty of cDNA preparation and lack of gene manipulation tools for basidiomycete fungi. To develop a versatile host for basidiomycete genes, we examined gene expression using genomic DNA sequences in the robust ascomycete host Aspergillus oryzae, which is frequently used for the production of metabolites from filamentous fungi. Exhaustive expression of 30 terpene synthase genes from the basidiomycetes Clitopilus pseudo-pinsitus and Stereum hirsutum showed two splicing patterns, i.e., completely spliced cDNAs giving terpenes (15 cases) and mostly spliced cDNAs, indicating that A. oryzae correctly spliced most introns at the predicted positions and lengths. The mostly spliced cDNAs were expressed after PCR-based removal of introns, resulting in the successful production of terpenes (14 cases). During this study, we observed relatively frequent mispredictions in the automated program. Hence, the complementary use of A. oryzae expression and automated prediction will be a powerful tool for genome mining.IMPORTANCE The recent large influx of genome sequences from basidiomycetes, which are prolific producers of bioactive natural products, may provide opportunities to develop novel drug candidates. The development of a reliable expression system is essential for the genome mining of natural products because of the lack of a tractable host for heterologous expression of basidiomycete genes. For this purpose, we applied the ascomycete Aspergillus oryzae system for the direct expression of fungal natural product biosynthetic genes from genomic DNA. Using this system, 29 sesquiterpene synthase genes and diterpene biosynthetic genes for bioactive pleuromutilin were successfully expressed. Together with the use of computational tools for intron prediction, this Aspergillus oryzae system represents a practical method for the production of basidiomycete natural products.

  36. Biosynthetic study of conidiation-inducing factor conidiogenone: heterologous production and cyclization mechanism of a key bifunctional diterpene synthase Peer-reviewed

    Tetsuya Shiina, Kazuya Nakagawa, Yukiko Fujisaki, Taro Ozaki, Chengwei Liu, Tomonobu Toyomasu, Masaru Hashimoto, Hiroyuki Koshino, Atsushi Minami, Hiroshi Kawaide, Hideaki Oikawa

    Bioscience, Biotechnology, and Biochemistry 83 (2) 192-201 2019/02/01

    Publisher: Informa {UK} Limited

    DOI: 10.1080/09168451.2018.1536518  

    ISSN: 1347-6947

  37. Identification of the common biosynthetic gene cluster for both antimicrobial streptoaminals and antifungal 5-alkyl-1,2,3,4-tetrahydroquinolines. International-journal Peer-reviewed

    Ozaki T, Sugiyama R, Shimomura M, Nishimura S, Asamizu S, Katsuyama Y, Kakeya H, Onaka H

    Organic & biomolecular chemistry 17 (9) 2370-2378 2019/01

    DOI: 10.1039/c8ob02846j  

    ISSN: 1477-0520

    More details Close

    5-Alkyl-1,2,3,4-tetrahydroquinolines (5aTHQs) and streptoaminals (STAMs) are natural products isolated from the combined-culture of Streptomyces nigrescens HEK616 and Tsukamurella pulmonis TP-B0596. Despite their unique structures, their biosynthetic pathway has yet to be elucidated. In the present study, we conducted a feeding experiment using 13C-labeled acetates and demonstrated that 5aTHQs are likely synthesized by the action of polyketide synthase (PKS). Based on this observation, we identified the biosynthetic gene cluster for 5aTHQs. Interestingly, the same gene cluster was also responsible for the structurally-distinct STAMs. The gene cluster contains nine genes encoding one acyl carrier protein, two sets of ketosynthases (KSs) and chain length factors (CLFs), one aminotransferase/reductase bifunctional protein, two ketoreductases, and one thioesterase. KSs and CLFs are classified into the phylogenetically distinct clades from those of known type II PKSs. Heterologous expression of the biosynthetic genes and subsequent gene inactivation clearly indicated that all of the nine genes were required for the biosynthesis of both compounds. In the proposed biosynthetic pathway, chain elongation by PKS, reductive cleavage of a thioester bond, and subsequent transamination generate the core skeleton of both compounds. Differences in the oxidation states of the products result in a distinct cyclization mode to yield 5aTHQs and STAMs.

  38. Heterologous production of asperipin-2a: proposal for sequential oxidative macrocyclization by a fungi-specific DUF3328 oxidase Peer-reviewed

    Ying Ye, Taro Ozaki, Myco Umemura, Chengwei Liu, Atsushi Minami, Hideaki Oikawa

    Organic & Biomolecular Chemistry 2019

    Publisher: Royal Society of Chemistry ({RSC})

    DOI: 10.1039/C8OB02824A  

    ISSN: 1477-0520

  39. Total Biosynthesis of Brassicicenes: Identification of a Key Enzyme for Skeletal Diversification Peer-reviewed

    Akihiro Tazawa, Ying Ye, Taro Ozaki, Chengwei Liu, Yasushi Ogasawara, Tohru Dairi, Yusuke Higuchi, Nobuo Kato, Katsuya Gomi, Atsushi Minami, Hideaki Oikawa

    Organic Letters 20 (19) 6178-6182 2018/10/05

    Publisher: American Chemical Society ({ACS})

    DOI: 10.1021/acs.orglett.8b02654  

    ISSN: 1523-7060

  40. Unveiling Biosynthesis of the Phytohormone Abscisic Acid in Fungi: Unprecedented Mechanism of Core Scaffold Formation Catalyzed by an Unusual Sesquiterpene Synthase Peer-reviewed

    Junya Takino, Takuto Kozaki, Yoshiro Sato, Chengwei Liu, Taro Ozaki, Atsushi Minami, Hideaki Oikawa

    Journal of the American Chemical Society 140 (39) 12392-12395 2018/10/03

    Publisher: American Chemical Society ({ACS})

    DOI: 10.1021/jacs.8b08925  

    ISSN: 0002-7863

  41. Cyclopentane-forming di/sesterterpene synthases: widely distributed enzymes in bacteria, fungi, and plants. Peer-reviewed

    Minami A, Ozaki T, Liu C, Oikawa H

    Natural product reports 2018/06

    DOI: 10.1039/c8np00026c  

    ISSN: 0265-0568

  42. Enzymatic Formation of a Skipped Methyl-Substituted Octaprenyl Side Chain of Longestin (KS-505a): Involvement of Homo-IPP as a Common Extender Unit Peer-reviewed

    Taro Ozaki, Sandip S. Shinde, Lei Gao, Ryo Okuizumi, Chengwei Liu, Yasushi Ogasawara, Xiaoguang Lei, Tohru Dairi, Atsushi Minami, Hideaki Oikawa

    Angewandte Chemie - International Edition 57 (22) 6629-6632 2018/05/28

    Publisher: Wiley-VCH Verlag

    DOI: 10.1002/anie.201802116  

    ISSN: 1521-3773 1433-7851

  43. Heterologous Biosynthesis of Fungal Indole Sesquiterpene Sespendole. International-journal Peer-reviewed

    Kudo K, Liu C, Matsumoto T, Minami A, Ozaki T, Toshima H, Gomi K, Oikawa H

    Chembiochem : a European journal of chemical biology 19 (14) 1492-1497 2018/05

    DOI: 10.1002/cbic.201800187  

    ISSN: 1439-4227

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    Indole sesquiterpene sespendole, which has been isolated from the filamentous fungus Pseudobotrytis terrestris FKA-25, is a specific inhibitor of lipid droplet synthesis in mouse macrophages. The biosynthetic pathway that involves genes encoding six enzymes (spdEMBQHJ) was elucidated through heterologous expression of spd genes in Aspergillus oryzae, biotransformation experiments, and in vitro enzymatic reactions with a recombinant protein, thereby revealing the mechanism underlying the characteristic modification on the indole ring, catalyzed by a set of prenyltransferase (SpdE)/cytochrome P450 (SpdJ) enzymes. Functional analysis of the homologous genes encoding these enzymes involved in the biosynthesis of lolitrem allowed a biosynthetic pathway for the bicyclic ring skeleton fused to the indole ring to be proposed.

  44. Identification of novel sesterterpenes by genome mining of phytopathogenic fungi Phoma and Colletotrichum sp. Peer-reviewed

    Lei Gao, Koji Narita, Taro Ozaki, Naoyoshi Kumakura, Pamela Gan, Atsushi Minami, Chengwei Liu, Xiaoguang Lei, Ken Shirasu, Hideaki Oikawa

    Tetrahedron Letters 59 (12) 1136-1139 2018/03/21

    Publisher: Elsevier Ltd

    DOI: 10.1016/j.tetlet.2018.02.022  

    ISSN: 1873-3581 0040-4039

  45. Total Biosynthesis of Antiangiogenic Agent (-)-Terpestacin by Artificial Reconstitution of the Biosynthetic Machinery in Aspergillus oryzae. Peer-reviewed

    Narita K, Minami A, Ozaki T, Liu C, Kodama M, Oikawa H

    The Journal of organic chemistry 83 (13) 7042-7048 2018/02

    DOI: 10.1021/acs.joc.7b03220  

    ISSN: 0022-3263

  46. Biosynthetic Machinery of Diterpene Pleuromutilin Isolated from Basidiomycete Fungi Peer-reviewed

    Momoka Yamane, Atsushi Minami, Chengwei Liu, Taro Ozaki, Ichiro Takeuchi, Tae Tsukagoshi, Tetsuo Tokiwano, Katsuya Gomi, Hideaki Oikawa

    CHEMBIOCHEM 18 (23) 2317-2322 2017/12

    DOI: 10.1002/cbic.201700434  

    ISSN: 1439-4227

    eISSN: 1439-7633

  47. Focused Genome Mining of Structurally Related Sesterterpenes: Enzymatic Formation of Enantiomeric and Diastereomeric Products Peer-reviewed

    Koji Narita, Hajime Sato, Atsushi Minami, Kosei Kudo, Lei Gao, Chengwei Liu, Taro Ozaki, Motoichiro Kodama, Xiaoguang Lei, Tohru Taniguchi, Kenji Monde, Mami Yamazaki, Masanobu Uchiyama, Hideaki Oikawa

    ORGANIC LETTERS 19 (24) 6696-6699 2017/12

    DOI: 10.1021/acs.orglett.7b03418  

    ISSN: 1523-7060

    eISSN: 1523-7052

  48. Structural Insights into the CotB2-Catalyzed Cyclization of Geranylgeranyl Diphosphate to the Diterpene Cyclooctat-9-en-7-ol Peer-reviewed

    Takeo Tomita, Seung-Young Kim, Kazuya Teramoto, Ayuko Meguro, Taro Ozaki, Ayako Yoshida, Yudai Motoyoshi, Naoki Mori, Ken Ishigami, Hidenori Watanabe, Makoto Nishiyama, Tomohisa Kuzuyama

    ACS CHEMICAL BIOLOGY 12 (6) 1621-1628 2017/06

    DOI: 10.1021/acschembio.7b00154  

    ISSN: 1554-8929

    eISSN: 1554-8937

  49. Biosynthetic Origin of the Hydroxamic Acid Moiety of Trichostatin A: Identification of Unprecedented Enzymatic Machinery Involved in Hydroxylamine Transfer Peer-reviewed

    Kei Kudo, Taro Ozaki, Kazuo Shin-ya, Makoto Nishiyama, Tomohisa Kuzuyama

    JOURNAL OF THE AMERICAN CHEMICAL SOCIETY 139 (20) 6799-6802 2017/05

    DOI: 10.1021/jacs.7b02071  

    ISSN: 0002-7863

  50. Dissection of goadsporin biosynthesis by in vitro reconstitution leading to designer analogues expressed in vivo Peer-reviewed

    Taro Ozaki, Kona Yamashita, Yuki Goto, Morito Shimomura, Shohei Hayashi, Shumpei Asamizu, Yoshinori Sugai, Haruo Ikeda, Hiroaki Suga, Hiroyasu Onaka

    NATURE COMMUNICATIONS 8 14207 2017/02

    DOI: 10.1038/ncomms14207  

    ISSN: 2041-1723

  51. Discovery and Total Synthesis of Streptoaminals: Antimicrobial [5,5]-Spirohemiaminals from the Combined-Culture of Streptomyces nigrescens and Tsukamurella pulmonis Peer-reviewed

    Ryosuke Sugiyama, Shinichi Nishimura, Taro Ozaki, Shumpei Asamizu, Hiroyasu Onaka, Hideaki Kakeya

    ANGEWANDTE CHEMIE-INTERNATIONAL EDITION 55 (35) 10278-10282 2016/08

    DOI: 10.1002/anie.201604126  

    ISSN: 1433-7851

    eISSN: 1521-3773

  52. Insights into the Biosynthesis of Dehydroalanines in Goadsporin Peer-reviewed

    Taro Ozaki, Yukari Kurokawa, Shohei Hayashi, Naoya Oku, Shumpei Asamizu, Yasuhiro Igarashi, Hiroyasu Onaka

    CHEMBIOCHEM 17 (3) 218-223 2016/02

    DOI: 10.1002/cbic.201500541  

    ISSN: 1439-4227

    eISSN: 1439-7633

  53. Mycolic acid-containing bacteria activate heterologous secondary metabolite expression in Streptomyces lividans Peer-reviewed

    Hiroyasu Onaka, Taro Ozaki, Yukiko Mori, Masumi Izawa, Shohei Hayashi, Shumpei Asamizu

    JOURNAL OF ANTIBIOTICS 68 (9) 594-597 2015/09

    DOI: 10.1038/ja.2015.31  

    ISSN: 0021-8820

  54. 5-Alkyl-1,2,3,4-tetrahydroquinolines, New Membrane-Interacting Lipophilic Metabolites Produced by Combined Culture of Streptomyces nigrescens and Tsukamurella pulmonis Peer-reviewed

    Ryosuke Sugiyama, Shinichi Nishimura, Taro Ozaki, Shumpei Asamizu, Hiroyasu Onaka, Hideaki Kakeya

    ORGANIC LETTERS 17 (8) 1918-1921 2015/04

    DOI: 10.1021/acs.orglett.5b00607  

    ISSN: 1523-7060

    eISSN: 1523-7052

  55. Killing of Mycolic Acid-Containing Bacteria Aborted Induction of Antibiotic Production by Streptomyces in Combined-Culture. International-journal Peer-reviewed

    Shumpei Asamizu, Taro Ozaki, Kanae Teramoto, Katsuya Satoh, Hiroyasu Onaka

    PloS one 10 (11) e0142372 2015

    DOI: 10.1371/journal.pone.0142372  

    More details Close

    Co-culture of Streptomyces with mycolic acid-containing bacteria (MACB), which we termed "combined-culture," alters the secondary metabolism pattern in Streptomyces and has been a useful method for the discovery of bioactive natural products. In the course of our investigation to identify the inducing factor(s) of MACB, we previously observed that production of pigments in Streptomyces lividans was not induced by factors such as culture extracts or mycolic acids. Although dynamic changes occurred in culture conditions because of MACB, the activation of pigment production by S. lividans was observed in a limited area where both colonies were in direct contact. This suggested that direct attachment of cells is a requirement and that components on the MACB cell membrane may play an important role in the response by S. lividans. Here we examined whether this response was influenced by dead MACB that possess intact mycolic acids assembled on the outer cell membrane. Formaldehyde fixation and γ-irradiation were used to prepare dead cells that retain their shape and mycolic acids of three MACB species: Tsukamurella pulmonis, Rhodococcus erythropolis, and Rhodococcus opacus. Culturing tests verified that S. lividans does not respond to the intact dead cells of three MACB. Observation of combined-culture by scanning electron microscopy (SEM) indicated that adhesion of live MACB to S. lividans mycelia were a significant interaction that resulted in formation of co-aggregation. In contrast, in the SEM analysis, dead cells were not observed to adhere. Therefore, direct attachment by live MACB cells is proposed as one of the possible factors that causes Streptomyces to alter its specialized metabolism in combined-culture.

  56. Crystallization and preliminary X-ray diffraction analysis of cyclolavandulyl diphosphate synthase, a new member of the cis-isoprenyl diphosphate synthase superfamily Peer-reviewed

    Takeo Tomita, Taro Ozaki, Kenichi Matsuda, Makoto Nishiyama, Tomohisa Kuzuyama

    Acta Crystallographica Section F:Structural Biology Communications 70 1410-1413 2014/10/01

    Publisher: International Union of Crystallography

    DOI: 10.1107/S2053230X14018883  

    ISSN: 2053-230X

  57. Crystallization and preliminary X-ray diffraction analysis of cyclolavandulyl diphosphate synthase, a new member of the cis-isoprenyl diphosphate synthase superfamily Peer-reviewed

    Takeo Tomita, Taro Ozaki, Kenichi Matsuda, Makoto Nishiyama, Tomohisa Kuzuyama

    ACTA CRYSTALLOGRAPHICA SECTION F-STRUCTURAL BIOLOGY COMMUNICATIONS 70 (Pt 10) 1410-1413 2014/10

    DOI: 10.1107/S2053230X14018883  

    ISSN: 1744-3091

  58. Genome Mining Reveals a Minimum Gene Set for the Biosynthesis of 32-Membered Macrocyclic Thiopeptides Lactazoles Peer-reviewed

    Shohei Hayashi, Taro Ozaki, Shumpei Asamizu, Haruo Ikeda, Satoshi Omura, Naoya Oku, Yasuhiro Igarashi, Hiroshi Tomoda, Hiroyasu Onaka

    CHEMISTRY & BIOLOGY 21 (5) 679-688 2014/05

    DOI: 10.1016/j.chembiol.2014.03.008  

    ISSN: 1074-5521

    eISSN: 1879-1301

  59. Cyclolavandulyl Skeleton Biosynthesis via Both Condensation and Cyclization Catalyzed by an Unprecedented Member of the cis-Isoprenyl Diphosphate Synthase Superfamily Peer-reviewed

    Taro Ozaki, Ping Zhao, Tetsuro Shinada, Makoto Nishiyama, Tomohisa Kuzuyama

    JOURNAL OF THE AMERICAN CHEMICAL SOCIETY 136 (13) 4837-4840 2014/04

    DOI: 10.1021/ja500270m  

    ISSN: 0002-7863

  60. Structure of the quinoline N-hydroxylating cytochrome P450 RauA, an essential enzyme that confers antibiotic activity on aurachin alkaloids Peer-reviewed

    Yoshiaki Yasutake, Wataru Kitagawa, Miyako Hata, Taiki Nishioka, Taro Ozaki, Makoto Nishiyama, Tomohisa Kuzuyama, Tomohiro Tamura

    FEBS LETTERS 588 (1) 105-110 2014/01

    DOI: 10.1016/j.febslet.2013.11.016  

    ISSN: 0014-5793

    eISSN: 1873-3468

  61. Genetic approaches to generate hyper-producing strains of goadsporin: the relationships between productivity and gene duplication in secondary metabolite biosynthesis Peer-reviewed

    Kentaro Haginaka, Shumpei Asamizu, Taro Ozaki, Yasuhiro Igarashi, Tamotsu Furumai, Hiroyasu Onaka

    BIOSCIENCE BIOTECHNOLOGY AND BIOCHEMISTRY 78 (3) 394-399 2014

    DOI: 10.1080/09168451.2014.885824  

    ISSN: 0916-8451

    eISSN: 1347-6947

  62. Cloning and heterologous expression of the aurachin RE biosynthesis gene cluster afford a new cytochrome P450 for quinoline N-hydroxylation Peer-reviewed

    Wataru Kitagawa, Taro Ozaki, Taiki Nishioka, Yoshiaki Yasutake, Miyako Hata, Makoto Nishiyama, Tomohisa Kuzuyama, Tomohiro Tamura

    ChemBioChem 14 (9) 1085-1093 2013/06

    DOI: 10.1002/cbic.201300167  

    ISSN: 1439-4227 1439-7633

  63. Novel Tryptophan Metabolism by a Potential Gene Cluster That Is Widely Distributed among Actinomycetes Peer-reviewed

    Taro Ozaki, Makoto Nishiyama, Tomohisa Kuzuyama

    JOURNAL OF BIOLOGICAL CHEMISTRY 288 (14) 9946-9956 2013/04

    DOI: 10.1074/jbc.M112.436451  

    ISSN: 0021-9258

  64. Production of Novel Antioxidative Prenyl Naphthalen-ols by Combinational Bioconversion with Dioxygenase PhnA1A2A3A4 and Prenyltransferase NphB or SCO7190 Peer-reviewed

    Kazutoshi Shindo, Ayako Tachibana, Ayumi Tanaka, Shizuka Toba, Emi Yuki, Taro Ozaki, Takuto Kumano, Makoto Nishiyama, Norihiko Misawa, Tomohisa Kuzuyama

    BIOSCIENCE BIOTECHNOLOGY AND BIOCHEMISTRY 75 (3) 505-510 2011/03

    DOI: 10.1271/bbb.100731  

    ISSN: 0916-8451

    eISSN: 1347-6947

  65. NovQ is a prenyltransferase capable of catalyzing the addition of a dimethylallyl group to both phenylpropanoids and flavonoids Peer-reviewed

    Taro Ozaki, Satoshi Mishima, Makoto Nishiyama, Tomohisa Kuzuyama

    JOURNAL OF ANTIBIOTICS 62 (7) 385-392 2009/07

    DOI: 10.1038/ja.2009.48  

    ISSN: 0021-8820

Show all ︎Show first 5

Misc. 193

  1. Heterologous production of the amatoxin precursor in Aspergillus oryzae

    根岸透子, 尾崎太郎, 菅原章公, 森下陽平, 浅井禎吾

    日本薬学会年会要旨集(Web) 144th 2024

    ISSN: 0918-9823

  2. Functional analysis of UstYa family proteins in the biosynthesis of cyclochlorotine derivatives

    岡本春太, 尾崎太郎, 森下陽平, 菅原章公, 浅井禎吾

    日本薬学会年会要旨集(Web) 144th 2024

    ISSN: 0918-9823

  3. Genome mining-based discovery of resorcinolic macrolides from Cytospora sp.

    長谷川智哉, 森下陽平, 菅原章公, 尾崎太郎, 浅井禎吾

    日本薬学会年会要旨集(Web) 144th 2024

    ISSN: 0918-9823

  4. Synthesis of polyketide-peptide hybrid-like macrocyclic compounds on DNA aimed at constructing DNA-encoded libraries.

    惟村壮哉, 菅原章公, 森下陽平, 尾崎太郎, 浅井禎吾

    日本薬学会年会要旨集(Web) 144th 2024

    ISSN: 0918-9823

  5. Chemoenzymatic synthesis of the fluorinated dolabellane skeleton for expanding functional diversity

    関谷光留, 佐藤史都, 菅原章公, 森下陽平, 尾崎太郎, 浅井禎吾

    日本薬学会年会要旨集(Web) 144th 2024

    ISSN: 0918-9823

  6. Heterologous production of β-amyrin, a biosynthetic precursor of glycyrrhizin, in Aspergillus oryzae

    平林薫歩, 尾崎太郎, 森下陽平, 菅原章公, 浅井禎吾

    日本薬学会年会要旨集(Web) 144th 2024

    ISSN: 0918-9823

  7. Identification and characterization of the biosynthetic gene cluster of myrocins

    藤木竣大, 佐藤史都, 園原照隆, 森下陽平, 菅原章公, 尾崎太郎, 浅井禎吾

    日本薬学会年会要旨集(Web) 144th 2024

    ISSN: 0918-9823

  8. Biosynthetic studies of anti-tuberculosis substance chlorflavonin

    古村翔, 尾崎太郎, 菅原章公, 森下陽平, 浅井禎吾

    日本薬学会年会要旨集(Web) 144th 2024

    ISSN: 0918-9823

  9. Discovery and Functional Analysis of a Novel Terpene Cyclase Involved in the Biosynthesis of Vinigrol

    佐藤史都, 塚田健人, 古村翔, 森下陽平, 菅原章公, 尾崎太郎, 浅井禎吾

    日本農芸化学会大会講演要旨集(Web) 2024 2024

    ISSN: 2186-7976

  10. Rapid reconstitution of fungal biosynthetic gene clusters in Aspergillus oryzae

    青木翔吾, 尾崎太郎, 菅原章公, 森下陽平, 浅井禎吾

    日本農芸化学会大会講演要旨集(Web) 2024 2024

    ISSN: 2186-7976

  11. Genome mining of UstYa family proteins invloved in the biosyntheis of cyclochlorotine derivatives

    岡本春太, 尾崎太郎, 森下陽平, 菅原章公, 浅井禎吾

    日本農芸化学会大会講演要旨集(Web) 2024 2024

    ISSN: 2186-7976

  12. ゲノム再編成による糸状菌Aspergillus nigerの二次代謝活性化法の検討

    天井涼太, 森下陽平, 河野宏光, 尾崎太郎, 菅原章公, 太田邦史, 浅井禎吾

    日本農芸化学会東北支部大会プログラム・講演要旨集 158th (CD-ROM) 2023

  13. 糸状菌非リボソームペプチド探索を指向した長鎖生合成遺伝子の麹菌内再構築法の検討

    青木翔吾, 尾崎太郎, 菅原章公, 森下陽平, 浅井禎吾

    日本農芸化学会東北支部大会プログラム・講演要旨集 158th (CD-ROM) 2023

  14. Biosynthetic study of pestalactams

    SHI Yue, 菅原章公, 尾崎太郎, 浅井禎吾

    日本薬学会年会要旨集(Web) 143rd 2023

    ISSN: 0918-9823

  15. Biosynthetic study on chaetophenols produced by a fungus Chaetomium indicum

    松井洸人, 塚田健人, 菅原章公, 尾崎太郎, 浅井禎吾

    日本薬学会年会要旨集(Web) 143rd 2023

    ISSN: 0918-9823

  16. Genome mining-based discovery of fungal macrolides from Aspergillus petrakii

    LI Yi, 菅原章公, 尾崎太郎, 浅井禎吾

    日本薬学会年会要旨集(Web) 143rd 2023

    ISSN: 0918-9823

  17. Biosynthetic study of hymeglusin

    廣川瑞樹, 森下陽平, 塚田健人, 菅原章公, 尾崎太郎, 浅井禎吾

    日本薬学会年会要旨集(Web) 143rd 2023

    ISSN: 0918-9823

  18. Structure elucidation and biosynthetic study of chaetodepsipeptins

    本間悠人, 菅原章公, 森下陽平, 塚田健人, 尾崎太郎, 浅井禎吾

    日本薬学会年会要旨集(Web) 143rd 2023

    ISSN: 0918-9823

  19. Characterization of the diterpene cyclases involved in the biosynthesis of Vinigrol

    佐藤史都, 森下陽平, 塚田健人, 古村翔, 菅原章公, 永田隆平, 葛山智久, 尾崎太郎, 浅井禎吾

    日本薬学会年会要旨集(Web) 143rd 2023

    ISSN: 0918-9823

  20. Aspergillus petrakii由来マクロライド生合成遺伝子クラスターの機能解析

    李屹, 森下陽平, 菅原章公, 尾崎太郎, 浅井禎吾

    日本薬学会東北支部大会講演要旨集 62nd 2023

  21. 麹菌を宿主とするグリチルリチン生産系の構築

    平林薫歩, 尾崎太郎, 森下陽平, 菅原章公, 浅井禎吾

    日本薬学会東北支部大会講演要旨集 62nd 2023

  22. 大規模ゲノム再編成を利用した糸状菌休眠遺伝子活性化研究

    天井涼太, 森下陽平, 河野宏光, 尾崎太郎, 菅原章公, 太田邦史, 浅井禎吾

    日本薬学会東北支部大会講演要旨集 62nd 2023

  23. アマトキシン類の異種生産系確立のためのプラットフォーム構築

    根岸透子, 尾崎太郎, 菅原章公, 森下陽平, 浅井禎吾

    日本薬学会東北支部大会講演要旨集 62nd 2023

  24. Total biosynthesis of the basidiomycete derived antitumor substance melleolide (2)

    深谷充功, 尾関美衣菜, 尾崎太郎, 永木愛一郎, 南篤志, 及川英秋

    日本化学会春季年会講演予稿集(Web) 103rd 2023

  25. Mechanistic Studies on the Late-Stage Modification Enzymes in the Biosynthesis of Phomoidride B

    瀧野純矢, 山本真太郎, 尾崎太郎, 永木愛一郎, 南篤志, 及川英秋

    日本化学会春季年会講演予稿集(Web) 103rd 2023

  26. Exploration and functional analysis of sesquiterpene biosynthetic genes based on comprehensive analysis of terpene synthase

    小林瑞季, 尾崎太郎, 橋本勝, 永木愛一郎, 南篤志, 及川英秋

    日本化学会春季年会講演予稿集(Web) 103rd 2023

  27. 糸状菌フラボノイド・クロロフラボニン生合成機構の解析と異種生産

    古村翔, 尾崎太郎, 菅原章公, 森下陽平, 浅井禎吾

    日本生薬学会年会講演要旨集 69th 2023

    ISSN: 0919-1992

  28. Total Biosynthesis of Phomoidride B: Identification and Characterization of Methyltransferase Catalyzing Bicyclic Ketal Formation

    瀧野純矢, 山本真太郎, 尾崎太郎, 永木愛一郎, 南篤志, 及川英秋, 及川英秋

    日本農芸化学会大会講演要旨集(Web) 2023 2023

    ISSN: 2186-7976

  29. アマトキシン類の生合成解明に向けた遺伝子資源の探索

    根岸透子, 尾崎太郎, 菅原章公, 森下陽平, 浅井禎吾

    日本生薬学会年会講演要旨集 69th 2023

    ISSN: 0919-1992

  30. Vinigrol骨格形成機構の解明を目指した環化中間体の網羅的な単離構造決定

    佐藤史都, 森下陽平, 塚田健人, 古村翔, 菅原章公, 尾崎太郎, 浅井禎吾

    日本生薬学会年会講演要旨集 69th 2023

    ISSN: 0919-1992

  31. 糸状菌デプシペプチドのポストゲノム型探索研究

    本間悠人, 菅原章公, 森下陽平, 塚田健人, 尾崎太郎, 浅井禎吾

    日本薬学会東北支部大会講演要旨集 61st 2022

  32. ゲノムマイニングによる糸状菌マクロライド類の探索

    李屹, 菅原章公, 尾崎太郎, 浅井禎吾

    日本薬学会東北支部大会講演要旨集 61st 2022

  33. Atranone類およびMyrocin類の生合成におけるジテルペン環化酵素の機能解析

    佐藤史都, 園原照隆, 森下陽平, 菅原章公, 尾崎太郎, 浅井禎吾

    日本薬学会東北支部大会講演要旨集 61st 2022

  34. chaetophenol類の生合成研究

    松井洸人, 塚田健人, 青木優, 菅原章公, 尾崎太郎, 浅井禎吾, 浅井禎吾

    日本薬学会東北支部大会講演要旨集 61st 2022

  35. Study on funiculosin biosynthesis

    小此木亮介, 菅原章公, 尾崎太郎, 浅井禎吾

    日本薬学会年会要旨集(Web) 142nd 2022

    ISSN: 0918-9823

  36. Investigation of terpen cyclase in atranone biosynthesis

    佐藤史都, 園原照隆, 森下陽平, 菅原章広, 尾崎太郎, 浅井禎吾

    日本薬学会年会要旨集(Web) 142nd 2022

    ISSN: 0918-9823

  37. Genome mining of UbiA-type sesqui terpene cyclases

    倉澤岳志, 園原照隆, 菅原章公, 尾崎太郎, 浅井禎吾

    日本薬学会年会要旨集(Web) 142nd 2022

    ISSN: 0918-9823

  38. Discovery of alternative chalcone biosynthetic machinery

    古村翔, 森下陽平, 菅原章公, 尾崎太郎, 浅井禎吾

    日本薬学会年会要旨集(Web) 142nd 2022

    ISSN: 0918-9823

  39. Stereochemical analysis of highly reducing polyketide syntheses

    瀧野純矢, 小谷明里, 尾崎太郎, YU Jie, GUO Yian, YE Tao, 南篤志, 及川英秋

    日本化学会春季年会講演予稿集(Web) 102nd 2022

  40. Biosynthetic study of prenylated aromatic polyketides chaetophenols

    松井洸人, 塚田健人, 青木優, 菅原章公, 尾崎太郎, 浅井禎吾, 浅井禎吾

    食品薬学シンポジウム講演要旨集 9th (CD-ROM) 2022

  41. Biosynthetic study of Vinigrol

    佐藤史都, 森下陽平, 塚田健人, 古村翔, 菅原章広, 永田隆平, 葛山智久, 尾崎太郎, 浅井禎吾

    食品薬学シンポジウム講演要旨集 9th (CD-ROM) 2022

  42. Study on the biosynthesis of pestalactam compounds with ε-lactam structure.

    SHI Yue, 菅原章公, 尾崎太郎, 浅井禎吾

    食品薬学シンポジウム講演要旨集 9th (CD-ROM) 2022

  43. 特異な酸化酵素による天然物の構造多様化戦略

    尾崎太郎

    日本農芸化学会東北支部大会プログラム・講演要旨集 2022 2022

  44. Biosynthetic study of Thermolides for mechanistic understanding of the catalytic domains

    小谷明里, 瀧野純矢, 尾崎太郎, 南篤志, 及川英秋

    日本農芸化学会大会講演要旨集(Web) 2022 2022

    ISSN: 2186-7976

  45. Biosynthetic study of hymeglusin skeletal formation

    廣川瑞樹, 森下陽平, 塚田健人, 菅原章公, 尾崎太郎, 浅井禎吾

    日本農芸化学会大会講演要旨集(Web) 2022 2022

    ISSN: 2186-7976

  46. Discovery of fungal depsipeptide based on genome mining and heterologous expression

    本間悠人, 菅原章公, 森下陽平, 塚田健人, 尾崎太郎, 浅井禎吾

    日本農芸化学会大会講演要旨集(Web) 2022 2022

    ISSN: 2186-7976

  47. Study on stereochemistry of fungal highly reducing polyketide syntheses

    瀧野純矢, 小谷明里, 尾崎太郎, YU Jie, GUO Yian, YE Tao, 南篤志, 及川英秋

    日本農芸化学会大会講演要旨集(Web) 2022 2022

    ISSN: 2186-7976

  48. Development of Versatile Heterologous Expression System for Genome Mining of Basidiomycete Natural Products

    南篤志, 尾崎太郎, 及川英秋

    月刊ファインケミカル 50 (4) 2021

    ISSN: 0913-6150

  49. Biosynthetic study of PR-toxin by CRISPR/Cas9 genome editing

    佐藤芳郎, 瀧野純矢, 尾崎太郎, LIU Chengwei, 南篤志, 及川英秋

    日本化学会春季年会講演予稿集(Web) 101st 2021

  50. Biosynthesis of phialotides possessing unique iterative substructure (1)

    瀧野純矢, 小谷明里, 尾崎太郎, 南篤志, 及川英秋

    日本化学会春季年会講演予稿集(Web) 101st 2021

  51. Studies on the Biosynthesis of Phomoidride B

    山本真太郎, 尾崎太郎, LIU Chengwei, 丸山潤一, 南篤志, 及川英秋

    日本化学会春季年会講演予稿集(Web) 101st 2021

  52. Biosynthetic study of anthraquinone dimer natural product isolated from filamentous fungi (4)

    深谷充功, 尾崎太郎, LIU Chengwei, 南篤志, 及川英秋

    日本化学会春季年会講演予稿集(Web) 101st 2021

  53. Genome mining of biologically active sesterterpenoids by heterologous expression in Aspergillus oryze-2-

    山本紘嵩, 佐藤優哉, 佐藤輝歩, 成田興司, 尾崎太郎, 南篤志, 及川英秋

    日本化学会春季年会講演予稿集(Web) 101st 2021

  54. Biosynthetic study on phomopsin A, a fungal mycotoxin (3)

    曽ヶ端花帆, 五十嵐祐也, 尾崎太郎, LIU Chengwei, 南篤志, 及川英秋

    日本化学会春季年会講演予稿集(Web) 101st 2021

  55. Biosynthetic study of host selective toxin ACR-toxin

    小谷明里, 瀧野純矢, 尾崎太郎, 望月進, 秋光和也, 南篤志, 及川英秋

    日本化学会春季年会講演予稿集(Web) 101st 2021

  56. Study on the biosynthesis of host-selective toxin ACR-toxin derived from citrus brown spot disease

    小谷明里, 瀧野純矢, 尾崎太郎, 望月進, 秋光和也, 南篤志, 及川英秋

    日本農芸化学会大会講演要旨集(Web) 2021 2021

    ISSN: 2186-7976

  57. Analysis of the post-translational modification reaction of the fungal ribosomal peptide, phomopsin A

    曽ケ端花帆, 五十嵐祐也, 尾崎太郎, LIU Chengwei, 南篤志, 及川英秋

    日本農芸化学会大会講演要旨集(Web) 2021 2021

    ISSN: 2186-7976

  58. Biosynthetic study of phialotides (1)

    瀧野純矢, 小谷明里, 尾崎太郎, 南篤志, 及川英秋

    日本農芸化学会大会講演要旨集(Web) 2021 2021

    ISSN: 2186-7976

  59. Biosynthetic study of PR-toxin by utilizing Aspergillus oryzae system (2)

    佐藤芳郎, 瀧野純矢, 尾崎太郎, LIU Chengwei, 南篤志, 及川英秋

    日本農芸化学会大会講演要旨集(Web) 2021 2021

    ISSN: 2186-7976

  60. Total biosynthesis of the basidiomycete derived antitumor substance meleolide

    尾関美衣菜, 長嶺翔太, 尾崎太郎, 河岸洋和, 丸山潤一, 南篤志, 及川英秋

    日本農芸化学会大会講演要旨集(Web) 2021 2021

    ISSN: 2186-7976

  61. Biosynthetic study on Fungal Maleic Anhydride ”Cordyanhydride” (2)

    江口桃香, 長嶺翔太, 尾崎太郎, LIU Chengwei, 南篤志, 及川英秋

    日本農芸化学会大会講演要旨集(Web) 2021 2021

    ISSN: 2186-7976

  62. Studies on the Biosynthesis of Phomoidride B (2)

    山本真太郎, 尾崎太郎, LIU Chengwei, 丸山潤一, 南篤志, 及川英秋

    日本農芸化学会大会講演要旨集(Web) 2021 2021

    ISSN: 2186-7976

  63. Efficient Reconstitution of Biosynthetic Machinery for Biologically Active Natural Products of Basidiomycota Fungi

    尾崎太郎, LIU Chengwei, 長嶺翔太, 西下純平, 小崎拓登, 曽ケ端花帆, 佐藤芳郎, 小谷明里, WU Jing, 河岸洋和, 丸山潤一, 南篤志, 及川英秋

    天然有機化合物討論会講演要旨集(Web) 62nd 2020

    ISSN: 2433-1856

  64. 酸無水物多量体Cordyanhydrideの生合成研究

    江口桃香, 長嶺翔太, 尾崎太郎, 劉成偉, 南篤志, 及川英秋

    日本農芸化学会北海道支部学術講演会講演要旨集(Web) 2020 2020

  65. 担子菌由来抗腫瘍物質melleolideの異種生産

    尾関美衣菜, 長嶺翔太, 尾崎太郎, 丸山潤一, 南篤志, 及川英秋

    日本農芸化学会北海道支部学術講演会講演要旨集(Web) 2020 2020

  66. コレステロール生合成阻害剤phomoidride Bの生合成研究

    山本真太郎, 尾崎太郎, 劉成偉, 丸山潤一, 南篤志, 及川英秋

    日本農芸化学会北海道支部学術講演会講演要旨集(Web) 2020 2020

  67. Heterologous expression of fungal sesquiterpenes by genome editing.

    水野上裕亮, 瀧野純矢, 尾崎太郎, LIU Chengwei, 丸山潤一, 南篤志, 及川英秋

    日本化学会春季年会講演予稿集(CD-ROM) 100th 2020

  68. Studies on the Biosynthesis of Phomoidride B

    山本真太郎, 尾崎太郎, LIU Chengwei, 丸山潤一, 南篤志, 及川英秋

    日本化学会春季年会講演予稿集(CD-ROM) 100th 2020

  69. Biosynthetic study of anthraquinone dimer natural product isolated from filamentous fungi

    深谷充功, 水野上裕亮, 南篤志, 尾崎太郎, LIU Chengwei, 及川英秋

    日本化学会春季年会講演予稿集(CD-ROM) 100th 2020

  70. Biosynthetic study of natural terpenoids derived from mushroom

    西下純平, 長嶺翔太, 尾崎太郎, LIU Chengwei, 丸山潤一, 南篤志, 及川英秋

    日本化学会春季年会講演予稿集(CD-ROM) 100th 2020

  71. Biosynthetic study on phomopsin A, a fungal mycotoxin (2)

    曽ヶ端花帆, 五十嵐祐也, 尾崎太郎, LIU Chengwei, 南篤志, 及川英秋

    日本化学会春季年会講演予稿集(CD-ROM) 100th 2020

  72. Biosynthetic study of PR-toxin by CRISPR/Cas9 genome editing

    佐藤芳郎, 瀧野純矢, LIU Chengwei, 尾崎太郎, 丸山潤一, 南篤志, 及川英秋

    日本化学会春季年会講演予稿集(CD-ROM) 100th 2020

  73. Biosynthetic study on antifungal agent zopfiellin (4)

    椎名哲也, 松優佑, 長嶺翔太, 尾崎太郎, LIU Chengwei, 南篤志, 及川英秋

    日本化学会春季年会講演予稿集(CD-ROM) 100th 2020

  74. Studies on Total Biosynthesis of Abscisic Acid and Unique cyclization mechanism

    瀧野純矢, 小崎拓登, 佐藤芳郎, 水野上裕亮, 劉成偉, 尾崎太郎, 南篤志, 及川英秋

    万有仙台シンポジウム 31st 2020

  75. Biosynthetic study of PR-toxin by utilizing Aspergillus oryzae expression system

    佐藤芳郎, 瀧野純矢, RYU Chengwei, 尾崎太郎, 丸山潤一, 南篤志, 及川英秋

    日本農芸化学会大会講演要旨集(Web) 2020 2020

    ISSN: 2186-7976

  76. Heterologous production of natural terpenoids derived from mushroom

    西下純平, 長嶺翔太, 尾崎太郎, LIU Chengwei, 丸山潤一, 南篤志, 及川英秋

    日本農芸化学会大会講演要旨集(Web) 2020 2020

    ISSN: 2186-7976

  77. Biosynthetic study of Abscisic Acid utilizing Aspergillus oryzae heterologous expression system (4)

    瀧野純矢, 小崎拓登, LIU Chengwei, 尾崎太郎, 南篤志, 及川英秋

    日本農芸化学会大会講演要旨集(Web) 2020 2020

    ISSN: 2186-7976

  78. Efficient Reconstitution of the Biosynthetic Pathway of Basidiomycota Diterpene Erinacines

    小谷明里, LIU Chengwei, 尾崎太郎, WU Jing, 河岸洋和, 丸山潤一, 南篤志, 及川英秋

    日本農芸化学会大会講演要旨集(Web) 2020 2020

    ISSN: 2186-7976

  79. Enzymatic Construction of Eight-membered ring in the zopfiellin biosynthesis

    椎名哲也, 松優佑, 長嶺翔太, 尾崎太郎, LIU Chengwei, 南篤志, 及川英秋

    日本農芸化学会大会講演要旨集(Web) 2020 2020

    ISSN: 2186-7976

  80. Biosynthetic Study of Melleolide from Basidiomycota Utilizing Heterologous Expression System (3)

    長嶺翔太, 南篤志, LIU Chengwei, 尾崎太郎, 丸山潤一, 及川英秋

    日本化学会春季年会講演予稿集(CD-ROM) 100th 2020

  81. Total Biosynthesis of Basidiomycota Diterpene Erinacines

    小谷明里, LIU Chengwei, 尾崎太郎, WU Jing, 河岸洋和, 丸山潤一, 南篤志, 及川英秋

    日本化学会春季年会講演予稿集(CD-ROM) 100th 2020

  82. Biosynthetic study of abscisic acid in fungi-2-

    瀧野純矢, 小崎拓登, LIU Chengwei, 尾崎太郎, 南篤志, 及川英秋

    日本化学会春季年会講演予稿集(CD-ROM) 100th 2020

  83. Total biosynthesis and structural diversification of fungal indole diterpene lolitrems

    蒋雨露, 尾崎太郎, 劉成偉, 丸山潤一, 南篤志, 及川英秋

    万有札幌シンポジウム 32nd 2020

  84. Total Biosynthesis of Biologically Active Natural Products Isolated from Fungi

    南篤志, 尾崎太郎, 及川英秋

    月刊ファインケミカル 49 (3) 2020

    ISSN: 0913-6150

  85. 糸状菌による植物ホルモンアブシジン酸の生合成・新奇な環化酵素の発見

    南篤志, 尾崎太郎, LIU Chengwei, 及川英秋

    バイオサイエンスとインダストリー 77 (2) 2019

    ISSN: 0914-8981

  86. 植物ホルモンアブシジン酸の全生合成と特異な環化機構の解明

    瀧野純矢, 小崎拓登, 劉成偉, 尾崎太郎, 南篤志, 及川英秋

    日本農芸化学会北海道支部講演会講演要旨(Web) 2019 2019

  87. 抗生物質zopfiellinの生合成研究(3)

    椎名哲也, 松優佑, 長嶺翔太, 尾崎太郎, 劉成偉, 南篤志, 及川英秋

    日本農芸化学会北海道支部講演会講演要旨(Web) 2019 2019

  88. 複合培養におけるStreptomyces sp.HEK616による5aTHQの生産機構

    浅水俊平, 尾崎太郎, 尾崎太郎, 西村慎一, 西村慎一, 掛谷秀昭, 尾仲宏康

    日本農芸化学会大会講演要旨集(Web) 2019 2019

    ISSN: 2186-7976

  89. 糸状菌が生産する酸無水物多量体の生合成に関する研究

    椎名哲也, 長嶺翔太, 松優佑, 尾崎太郎, LIU Chengwei, 南篤志, 及川英秋

    日本農芸化学会大会講演要旨集(Web) 2019 2019

    ISSN: 2186-7976

  90. 植物ホルモンAbscisic Acidの生合成における新規環化酵素の機能解析-1-

    瀧野純矢, 小崎拓登, 佐藤芳郎, LIU Chengwei, 尾崎太郎, 南篤志, 及川英秋

    日本農芸化学会大会講演要旨集(Web) 2019 2019

    ISSN: 2186-7976

  91. キノコ由来テルペン系天然物の汎用的な生産法の開発-3-

    長嶺翔太, 西下純平, LIU Chengwei, 尾崎太郎, 丸山潤一, 南篤志, 及川英秋

    日本農芸化学会大会講演要旨集(Web) 2019 2019

    ISSN: 2186-7976

  92. ロンゲスチン生合成における特異なメチル基導入機構の解明

    尾崎太郎, SHINDE Sandip S., GAO Lei, 奥泉諒, LIU Chengwei, 小笠原泰志, 大利徹, 南篤志, 及川英秋

    日本農芸化学会大会講演要旨集(Web) 2019 2019

    ISSN: 2186-7976

  93. ゲノム編集技術CRISPR/Cas9を用いた糸状菌天然物の異種生産(2)

    曽ケ端花帆, 尾崎太郎, LIU Chengwei, 丸山潤一, 南篤志, 及川英秋

    日本農芸化学会大会講演要旨集(Web) 2019 2019

    ISSN: 2186-7976

  94. 担子菌がもつセスキテルペン環化酵素の網羅的解析-2-

    長嶺翔太, 西下純平, LIU Chengwei, 尾崎太郎, 丸山潤一, 南篤志, 及川英秋

    日本化学会春季年会講演予稿集(CD-ROM) 99th 2019

  95. 糸状菌におけるアブシジン酸の生合成研究-1-

    瀧野純矢, 小崎拓登, 佐藤芳郎, LIU Chengwei, 尾崎太郎, 南篤志, 及川英秋

    日本化学会春季年会講演予稿集(CD-ROM) 99th 2019

  96. 担子菌がもつセスキテルペン環化酵素の網羅的解析-1-

    西下純平, 長嶺翔太, 小崎拓登, LIU Chengwei, 尾崎太郎, 丸山潤一, 南篤志, 及川英秋

    日本化学会春季年会講演予稿集(CD-ROM) 99th 2019

  97. 抗生物質Zopfiellinの生合成研究(2)

    椎名哲也, 長嶺翔太, 松優佑, 尾崎太郎, LIU Chengwei, 南篤志, 及川英秋

    日本化学会春季年会講演予稿集(CD-ROM) 99th 2019

  98. Streptomyces sp.HEK616とTsukamurella pulmonisとの複合培養での二次代謝活性化機構の解析

    浅水俊平, 浅水俊平, 尾崎太郎, 西村慎一, 掛谷秀昭, 尾仲宏康, 尾仲宏康

    日本放線菌学会大会講演要旨集 34th 2019

  99. 糸状菌が生産するアントラキノン類の生合成研究-2-

    深谷充功, 南篤志, 尾崎太郎, LIU Chengwei, 丸山潤一, 及川英秋

    日本化学会春季年会講演予稿集(CD-ROM) 99th 2019

  100. キノコ由来テルペン系天然物の汎用的な生産法の開発-2-

    西下純平, 長嶺翔太, 小崎拓登, LIU Chengwei, 尾崎太郎, 丸山潤一, 南篤志, 及川英秋

    日本農芸化学会大会講演要旨集(Web) 2019 2019

    ISSN: 2186-7976

  101. キノコ由来テルペン系天然物の汎用的な生産法の開発-1-

    LIU Chengwei, 佐藤芳郎, 尾崎太郎, WU Jing, 丸山潤一, 南篤志, 河岸洋和, 及川英秋

    日本農芸化学会大会講演要旨集(Web) 2019 2019

    ISSN: 2186-7976

  102. 糸状菌アントラキノン系ポリケタイドの生合成に関わる酵素遺伝子の機能解析-2-

    深谷充功, 南篤志, 尾崎太郎, LIU Chengwei, 丸山潤一, 及川英秋

    日本農芸化学会大会講演要旨集(Web) 2019 2019

    ISSN: 2186-7976

  103. 新規ラビオネン構造の形成に関与するランチペプチド合成酵素の解析—Analysis of lanthipeptide biosynthetic enzymes responsible for formation of novel goadionin structure—平成24年度寄付講座助成

    菅井 佳宣, 尾﨑 太郎, 浅水 俊平, 尾仲 宏康

    Research communications = 発酵研究所研究報告 (32) 167-177 2018

    Publisher: 大阪 : 発酵研究所

    ISSN: 0073-8751

  104. ミコール酸含有細菌に対する放線菌二次代謝応答機構の網羅的転写解析—RNA sequencing analysis of contact-dependent secondary metabolism responses by Streptomyces coelicolor—平成24年度寄付講座助成

    浅水 俊平, 尾﨑 太郎, 菅井 佳宣, 尾仲 宏康

    Research communications = 発酵研究所研究報告 (32) 87-94 2018

    Publisher: 大阪 : 発酵研究所

    ISSN: 0073-8751

  105. ゴードスポリン作用機構の解析—Goadsporin, a specific inhibitor of actinomycetal signal recognition particle—平成24年度寄付講座助成

    尾﨑 太郎, 菅井 佳宜, 浅水 俊平, 尾仲 宏康

    Research communications = 発酵研究所研究報告 (32) 129-139 2018

    Publisher: 大阪 : 発酵研究所

    ISSN: 0073-8751

  106. In vitro再構成系を用いたゴードスポリン生合成酵素の解析と合理的な類縁体設計—Dissection of goadsporin biosynthetic machinery by in vitro reconstitution leading to in vivo production of designer analogues—平成24年度寄付講座助成

    尾﨑 太郎, 菅井 佳宣, 浅水 俊平, 尾仲 宏康

    Research communications = 発酵研究所研究報告 (32) 141-154 2018

    Publisher: 大阪 : 発酵研究所

    ISSN: 0073-8751

  107. ゲノム探索による32員環新規チオペプチドラクタゾールの発見—Genome mining reveals a minimum gene set for the biosynthesis of 32-membered macrocyclic thiopeptides lactazoles—平成24年度寄付講座助成

    林 昌平, 尾﨑 太郎, 浅水 俊平, 尾仲 宏康

    Research communications = 発酵研究所研究報告 (32) 155-166 2018

    Publisher: 大阪 : 発酵研究所

    ISSN: 0073-8751

  108. 糸状菌テルペン環化酵素遺伝子のゲノムマイニングによる新規天然物の生産

    南篤志, 尾崎太郎, LIU Chengwei, 及川英秋

    バイオサイエンスとインダストリー 76 (1) 2018

    ISSN: 0914-8981

  109. 糸状菌由来リボソーマルペプチドRiPPSの生合成機構

    及川英秋, 南篤志, 尾崎太郎

    日本農芸化学会大会講演要旨集(Web) 2018 2018

    ISSN: 2186-7976

  110. 糸状菌が生産するインドールセスキテルペンの生合成研究(3)

    工藤洸星, 松本知之, LIU Chengwei, 尾崎太郎, 五味勝也, 南篤志, 及川英秋

    日本農芸化学会大会講演要旨集(Web) 2018 2018

    ISSN: 2186-7976

  111. 糸状菌アントラキノン系ポリケタイドの生合成に関わる酵素遺伝子の機能解析

    深谷充功, 南篤志, 尾崎太郎, LIU Chengwei, 丸山潤一, 及川英秋

    日本農芸化学会大会講演要旨集(Web) 2018 2018

    ISSN: 2186-7976

  112. ゲノム編集技術CRISPR/Cas9を用いた糸状菌天然物の異種生産

    佐藤優哉, 瀧野純矢, 椎名哲也, 鵜飼孝大, 南篤志, 尾崎太郎, LIU Chengwei, 藤井勲, 丸山潤一, 及川英秋

    日本農芸化学会大会講演要旨集(Web) 2018 2018

    ISSN: 2186-7976

  113. 生合成系の再構築によるセスキテルペンのゲノムマイニング

    瀧野純矢, 南篤志, 尾崎太郎, LIU Chengwei, 白須賢, 及川英秋

    日本化学会春季年会講演予稿集(CD-ROM) 98th 2018

  114. ゲノムマイニングによるコニジオゲノン生合成遺伝子の同定

    椎名哲也, 尾崎太郎, LIU Chengwei, 越野広雪, 南篤志, 及川英秋

    日本化学会春季年会講演予稿集(CD-ROM) 98th 2018

  115. 糸状菌が生産するアントラキノンダイマーの生合成研究

    深谷充功, 南篤志, 尾崎太郎, LIU Chengwei, 丸山潤一, 及川英秋

    日本化学会春季年会講演予稿集(CD-ROM) 98th 2018

  116. シクロヘルミントール類生合成酵素遺伝子の機能解析

    鵜飼孝大, 南篤志, 田中静也, 尾崎太郎, LIU Chengwei, 橋本勝, 及川英秋

    日本化学会春季年会講演予稿集(CD-ROM) 98th 2018

  117. Genome mining reveals a minimum gene set for the biosynthesis of 32-membered macrocyclic thiopeptides lactazoles.

    林昌平, 林昌平, 尾崎太郎, 尾崎太郎, 浅水俊平, 尾仲宏康, 大村智, 供田洋, 池田治生, 奥直也, 五十嵐康弘

    Institute for Fermentation, Osaka. Research Communications (32) 2018

    ISSN: 0073-8751

  118. Requirement of live mycolic acid-containing bacteria for induction of antibiotic production by Streptomyces in combined-culture

    浅水俊平, 尾崎太郎, 尾仲宏康, 佐藤勝也, 寺本華奈江, 寺本華奈江

    Institute for Fermentation, Osaka. Research Communications (32) 2018

    ISSN: 0073-8751

  119. Analysis of response deficient mutants of Streptomyces coelicolor generated by heavy ion beam induced mutagenesis to contact-dependent stimuli by Tsukamurella pulmonis

    浅水俊平, 菅井佳宣, 尾崎太郎, 尾仲宏康, 佐藤勝也, 大野豊

    Institute for Fermentation, Osaka. Research Communications (32) 2018

    ISSN: 0073-8751

  120. 異種発現によるバナナ病原菌由来ジテルペン類の生合成研究

    田澤聡大, YE Ying, 尾崎太郎, LIU Chengwei, 南篤志, 小笠原泰志, 大利徹, 及川英秋

    日本農芸化学会大会講演要旨集(Web) 2018 2018

    ISSN: 2186-7976

  121. 二次代謝誘導ペプチドgoadsporinの作用機構

    金田彬, 尾崎太郎, 菅井佳宣, 浅水俊平, 千田俊哉, 尾仲宏康

    日本農芸化学会大会講演要旨集(Web) 2018 2018

    ISSN: 2186-7976

  122. 病原性糸状菌が感染時特異的に生産するセスキテルペンの生合成研究

    瀧野純矢, 南篤志, 尾崎太郎, LIU Chengwei, 白須賢, 及川英秋

    日本農芸化学会大会講演要旨集(Web) 2018 2018

    ISSN: 2186-7976

  123. 麹菌異種発現系を用いたコニジオゲノンの異種生産

    椎名哲也, 尾崎太郎, LIU Chengwei, 越野広雪, 南篤志, 及川英秋

    日本農芸化学会大会講演要旨集(Web) 2018 2018

    ISSN: 2186-7976

  124. CRISPR/Cas9システムを用いた糸状菌由来天然物の異種生産

    佐藤優哉, 瀧野純矢, 椎名哲也, 鵜飼孝大, 南篤志, 尾崎太郎, LIU Chengwei, 藤井勲, 丸山潤一, 及川英秋

    日本化学会春季年会講演予稿集(CD-ROM) 98th 2018

  125. CRISPR/Cas9Systemを用いたcyclochlorotineの生合成研究

    YE Ying, LIU Chengwei, 尾崎太郎, 南篤志, 丸山潤一, 及川英秋

    日本農芸化学会大会講演要旨集(Web) 2018 2018

    ISSN: 2186-7976

  126. 糸状菌が生産するcyclohelminthol類の生合成研究

    鵜飼孝大, 南篤志, 田中静也, LIU Chengwei, 尾崎太郎, 橋本勝, 及川英秋

    日本農芸化学会大会講演要旨集(Web) 2018 2018

    ISSN: 2186-7976

  127. RNA sequencing analysis of contact-dependent secondary metabolism responses by Streptomyces coelicolor

    浅水俊平, 尾崎太郎, 菅井佳宣, 尾仲宏康, 佐々木槇子, 吉田昭介, 吉田昭介, 宮本憲二

    Institute for Fermentation, Osaka. Research Communications (32) 2018

    ISSN: 0073-8751

  128. Dissection of goadsporin biosynthetic machinery by in vitro reconstitution leading to in vivo production of designer analogues

    尾崎太郎, 尾崎太郎, 菅井佳宣, 浅水俊平, 尾仲宏康, 後藤佑樹, 菅裕明, 池田治生

    Institute for Fermentation, Osaka. Research Communications (32) 2018

    ISSN: 0073-8751

  129. Analysis of lanthipeptide biosynthetic enzymes responsible for formation of novel goadionin structure.

    菅井佳宣, 菅井佳宣, 尾崎太郎, 尾崎太郎, 浅水俊平, 尾仲宏康, 菅裕明, 後藤佑樹

    Institute for Fermentation, Osaka. Research Communications (32) 2018

    ISSN: 0073-8751

  130. Goadsporin, a specific inhibitor of actinomycetal signal recognition particle.

    尾崎太郎, 尾崎太郎, 菅井佳宜, 浅水俊平, 尾仲宏康

    Institute for Fermentation, Osaka. Research Communications (32) 2018

    ISSN: 0073-8751

  131. Membrane Affinity and Biological Activities of 5aTHQs, Combined-culture Metabolites

    西村慎一, 西村慎一, 杉山龍介, 仲谷崇宏, 尾崎太郎, 浅水俊平, 尾仲宏康, 掛谷秀昭

    天然有機化合物討論会講演要旨集(Web) 60th 2018

    ISSN: 2433-1856

  132. Studies on the Biosynthesis and Heterologous Production of Fungal Terpenoids

    尾崎太郎, 山根桃華, 田澤聡大, YE Ying, LIU Chengwei, 小笠原泰志, 大利徹, 南篤志, 及川英秋

    天然有機化合物討論会講演要旨集(Web) 60th 2018

    ISSN: 2433-1856

  133. バナナ病原菌が感染時に生産するジテルペン類の異種生産

    田澤聡大, YE Ying, 尾崎太郎, LIU Chengwei, 南篤志, 小笠原泰志, 大利徹, 及川英秋

    日本化学会春季年会講演予稿集(CD-ROM) 98th 2018

  134. Studies on the biosynthesis of novel alkaloids derived from the combined-culture of Streptomyces nigrescens HEK616 and Tsukamurella pulmonis

    尾崎太郎, 尾崎太郎, 浅水俊平, 尾仲宏康, 杉山龍介, 西村慎一, 掛谷秀昭

    Institute for Fermentation, Osaka. Research Communications (32) 2018

    ISSN: 0073-8751

  135. 天然ペプチド骨格の合理的な設計手法の開発

    尾崎太郎, 尾仲宏康, 菅裕明

    酵素工学ニュ-ス (78) 2017

    ISSN: 0911-9957

  136. 転移RNAのいろいろな機能

    尾崎太郎

    生物工学会誌 95 (4) 2017

    ISSN: 0919-3758

  137. 多様なリボゾーム翻訳後修飾ペプチド(RiPPs)の試験管内生合成

    尾崎太郎, 後藤佑樹, 尾仲宏康

    バイオサイエンスとインダストリー 75 (6) 2017

    ISSN: 0914-8981

  138. 糸状菌が生産するインドールセスキテルペン,セスペンドールの生合成研究(2)

    工藤洸星, 松本知之, LIU Chengwei, 尾崎太郎, 五味勝也, 南篤志, 及川英秋

    日本化学会春季年会講演予稿集(CD-ROM) 97th 2017

  139. 異種発現系を用いた繰り返し型PKS-NRPSの機能解析-1-

    鵜飼孝大, 南篤志, 尾崎太郎, 山根桃華, LIU Chengwei, 及川英秋

    日本化学会春季年会講演予稿集(CD-ROM) 97th 2017

  140. ustiloxin系糸状菌RiPPsのゲノムマイニング

    五十嵐祐也, YE Ying, 尾崎太郎, 南篤志, 五味勝也, 及川英秋

    日本農芸化学会大会講演要旨集(Web) 2017 2017

    ISSN: 2186-7976

  141. 麹菌異種発現系を用いたPKS-NRPS由来天然物の生合成研究

    LIU Chengwei, 山根桃華, 尾崎太郎, 南篤志, 及川英秋

    日本農芸化学会大会講演要旨集(Web) 2017 2017

    ISSN: 2186-7976

  142. 複合培養によって生産されるテトラヒドロキノリン化合物の解析

    下村杜人, 尾崎太郎, 杉山龍介, 西村慎一, 浅水俊平, 掛谷秀昭, 尾仲宏康

    日本放線菌学会大会講演要旨集 32nd 2017

  143. 異種発現系を用いた担子菌由来メレオライド類の生合成研究(1)

    長嶺翔太, 南篤志, LIU Chengwei, 尾崎太郎, 及川英秋

    日本化学会春季年会講演予稿集(CD-ROM) 97th 2017

  144. 合成生物学的手法を用いた糸状菌由来ポリケタイドの全生合成研究

    鵜飼孝大, 南篤志, 尾崎太郎, 劉成偉, 及川英秋

    万有札幌シンポジウム 29th 2017

  145. 薬剤ターゲットをFfhとするゴードスポリンの新規作用機構解析

    金田彬, 尾崎太郎, 菅井佳宣, 浅水俊平, 千田俊哉, 尾仲宏康

    日本農芸化学会大会講演要旨集(Web) 2017 2017

    ISSN: 2186-7976

  146. 試験管内完全合成系によるゴードスポリン生合成経路の解析とデザイナーアナログ創製

    尾仲宏康, 尾崎太郎, 山下湖奈, 後藤佑樹, 下村杜人, 林昌平, 浅水俊平, 菅井佳宣, 菅裕明

    日本農芸化学会大会講演要旨集(Web) 2017 2017

    ISSN: 2186-7976

  147. 抗生物質プロイロムチリンの生合成研究(3)

    山根桃華, 南篤志, LIU Chengwei, 尾崎太郎, 塚越多映, 常盤野哲生, 五味勝也, 及川英秋

    日本化学会春季年会講演予稿集(CD-ROM) 97th 2017

  148. 担子菌由来抗腫瘍性セスキテルペン・メレオライドの生合成研究

    長嶺翔太, 南篤志, LIU Chengwei, 尾崎太郎, 及川英秋

    メディシナルケミストリーシンポジウム講演要旨集 35th 2017

    ISSN: 0919-214X

  149. リボソームが作るペプチド系天然物の生合成

    尾崎太郎

    化学と工業 70 (10) 2017

    ISSN: 0022-7684

  150. 複合培養特異的に生産されるテトラヒドロキノリン生合成遺伝子の解析

    下村杜人, 尾崎太郎, 杉山龍介, 西村慎一, 浅水俊平, 掛谷秀昭, 尾仲宏康

    日本農芸化学会大会講演要旨集(Web) 2016 2016

    ISSN: 2186-7976

  151. RNA-seqによるミコール酸含有細菌に対するStreptomyces coelicolor A3(2)の応答解析

    佐々木槇子, 浅水俊平, 尾崎太郎, 宮本憲二, 尾仲宏康

    日本農芸化学会大会講演要旨集(Web) 2016 2016

    ISSN: 2186-7976

  152. 二次代謝誘導物質ゴードスポリン作用機構の解析

    尾崎太郎, 浅水俊平, 尾仲宏康

    日本農芸化学会大会講演要旨集(Web) 2016 2016

    ISSN: 2186-7976

  153. 放線菌由来新奇テルペン環化酵素の結晶構造解析

    小林正弥, 尾崎太郎, 富田武郎, 西山真, 葛山智久

    日本放線菌学会大会講演要旨集 31st 2016

  154. 複合培養におけるStreptomyces coelicolor A3(2)の経時的トランスクリプトーム解析

    浅水俊平, 佐々木槇子, 尾崎太郎, 菅井佳宣, 宮本憲二, 尾仲宏康

    日本放線菌学会大会講演要旨集 31st 2016

  155. 脂質結合性天然物の活用-放線菌複合培養液より見出した新規アルカロイド群に関する研究

    杉山龍介, 西村慎一, 尾崎太郎, 浅水俊平, 尾仲宏康, 掛谷秀昭

    日本薬学会年会要旨集(CD-ROM) 136th 2016

  156. 微生物の複合培養で得られる5aTHQとstreptoaminalの構造と機能

    西村慎一, 杉山龍介, 仲谷崇宏, 尾崎太郎, 浅水俊平, 尾仲宏康, 掛谷秀昭

    天然薬物の開発と応用シンポジウム講演要旨集 21st 2016

    ISSN: 0919-2085

  157. 無細胞翻訳後系を利用したゴードスポリン生合成経路の再構成と新奇アナログの創製

    尾崎太郎, 山下湖奈, 下村杜人, 後藤佑樹, 菅井佳宣, 浅水俊平, 菅裕明, 尾仲宏康

    日本放線菌学会大会講演要旨集 31st 2016

  158. 無細胞翻訳系を用いたラクタゾールの試験管内再構成系の確立

    下村杜人, 尾崎太郎, 菅井佳宣, 浅水俊平, 山下湖奈, 後藤佑樹, 菅裕明, 尾仲宏康

    日本放線菌学会大会講演要旨集 31st 2016

  159. ゴードスポリンの酵素的全合成

    山下湖奈, 尾崎太郎, 浅水俊平, 後藤佑樹, 菅裕明, 尾仲宏康

    日本農芸化学会大会講演要旨集(Web) 2016 2016

    ISSN: 2186-7976

  160. アリル基質同士の縮合と環化反応を触媒する新奇テルペン合成酵素の発見

    小林正弥, 尾崎太郎, 趙平, 富田武郎, 苅田祐馬, 保野陽子, 西村栄治, 品田哲郎, 西山真, 葛山智久

    イソプレノイド研究会例会講演要旨集 25th 11 2015/09/14

  161. 二次代謝誘導物質ゴードスポリンの作用機構の解析

    尾崎太郎, 浅水俊平, 尾仲宏康

    日本農芸化学会大会講演要旨集(Web) 2015 2015

    ISSN: 2186-7976

  162. goadsporin生合成機構を利用したgoadsporin倍加ペプチドの生産

    岡本悠志, 尾崎太郎, 浅水俊平, 尾仲宏康

    日本農芸化学会大会講演要旨集(Web) 2015 2015

    ISSN: 2186-7976

  163. 複合培養における放線菌二次代謝の誘導要因の探索

    浅水俊平, 尾崎太郎, 佐藤勝也, 尾仲宏康

    日本農芸化学会大会講演要旨集(Web) 2015 2015

    ISSN: 2186-7976

  164. Streptomyces sp.TP-A0584株由来ゴードスポリン生合成のin vitro再構成

    山下湖奈, 尾崎太郎, 浅水俊平, 後藤佑樹, 菅裕明, 尾仲宏康

    日本農芸化学会大会講演要旨集(Web) 2015 2015

    ISSN: 2186-7976

  165. Streptomyces sp.TP-A0584由来ランチペプチド系化合物のゲノムマイニングによる同定

    小野拓人, 江畑一真, 浅水俊平, 尾崎太郎, 尾仲宏康

    日本農芸化学会大会講演要旨集(Web) 2015 2015

    ISSN: 2186-7976

  166. 複合培養における放線菌とミコール酸含有菌の生死で異なる相互作用

    浅水俊平, 尾崎太郎, 寺本華奈江, 佐藤勝也, 尾仲宏康

    日本放線菌学会大会講演要旨集 30th 2015

  167. 二次代謝誘導物質ゴードスポリン作用機構の解析

    尾崎太郎, 浅水俊平, 尾仲宏康

    日本放線菌学会大会講演要旨集 30th 2015

  168. Streptomyces sp.TP-A0584由来ゴードスポリン生合成の試験管内再構成系の確立

    山下湖奈, 尾崎太郎, 浅水俊平, 後藤佑樹, 菅裕明, 尾仲宏康

    日本放線菌学会大会講演要旨集 30th 2015

  169. 新しいトリプトファン代謝経路を放線菌から発見 放線菌由来プレニル化インドールの生合成経路の解明

    尾崎太郎, 尾崎太郎, 葛山智久

    化学と生物 52 (3) 2014

    ISSN: 0453-073X

  170. Discovery of unusual isoprenyl diphosphate synthase that expands structural diversity of terpenoids

    72 (5) 412-414 2014

    Publisher: バイオインダストリー協会

    ISSN: 0914-8981

  171. テトラヒドロキノリン骨格を有する新規放線菌代謝物の構造多様性と生物活性

    杉山龍介, 西村慎一, 尾崎太郎, 尾仲宏康, 掛谷秀昭

    日本薬学会年会要旨集(CD-ROM) 134th 2014

  172. 放線菌由来プレニルカルバゾール類縁体生合成遺伝子の同定

    小林正弥, 尾崎太郎, 新家一男, 西山真, 葛山智人

    日本ゲノム微生物学会年会要旨集 8th 2014

  173. 放線菌の生産するプレニルインドールアルカロイドの生合成

    小林正弥, 尾崎太郎, 新家一男, 西山真, 葛山智久

    日本放線菌学会大会講演要旨集 29th 2014

  174. 複合培養を利用した新規テトラヒドロキノリン類の単離とその生合成に関する研究

    尾崎太郎, 杉山龍介, 西村慎一, 浅水俊平, 掛谷秀昭, 尾仲宏康

    日本放線菌学会大会講演要旨集 29th 2014

  175. 死細胞は放線菌の二次代謝を複合培養において誘導しない

    浅水俊平, 尾崎太郎, 尾仲宏康

    日本放線菌学会大会講演要旨集 29th 2014

  176. 放線菌の生産するプレニルカルバゾール類縁体の生合成研究

    小林正弥, 尾崎太郎, 新家一男, 西山真, 葛山智久

    日本農芸化学会大会講演要旨集(Web) 2014 2014

    ISSN: 2186-7976

  177. 複合培養において死細胞は放線菌の二次代謝を誘導しない

    浅水俊平, 尾崎太郎, 尾仲宏康

    日本農芸化学会大会講演要旨集(Web) 2014 2014

    ISSN: 2186-7976

  178. 放線菌の複合培養法による新規テトラヒドロキノリン類の単離とその生合成

    尾崎太郎, 森夕希子, 杉山龍介, 西村慎一, 浅水俊平, 掛谷秀昭, 尾仲宏康

    日本農芸化学会大会講演要旨集(Web) 2014 2014

    ISSN: 2186-7976

  179. ゲノム探索が明らかにした新規32員環チオペプチド,ラクタゾールの構造と生合成

    林昌平, 尾崎太郎, 浅水俊平, 尾仲宏康

    天然有機化合物討論会講演要旨集(Web) 56th 2014

    ISSN: 2433-1856

  180. ロドコッカス属由来抗生物質aurachin REの生合成遺伝子解析

    北川 航, 尾崎 太郎, 安武 義晃, 西山 真, 葛山 智久, 田村 具博

    日本放線菌学会大会講演要旨集 28回 64-64 2013/09

    Publisher: 日本放線菌学会

  181. 二次代謝誘導物質ゴードスポリン耐性化機構の解析

    尾崎太郎, 浅水俊平, 尾仲宏康

    日本放線菌学会大会講演要旨集 28th 2013

  182. 複合培養に応答するgodAプロモーター領域の解析

    浅水俊平, 小野拓人, 林昌平, 尾崎太郎, 尾仲宏康

    日本放線菌学会大会講演要旨集 28th 2013

  183. ラバンドシアニン生合成における新奇プレニルジリン酸合成酵素の同定と機能解析

    尾崎太郎, ZHAO Ping, 葛山智久, 西山真

    日本農芸化学会大会講演要旨集(Web) 2013 2013

    ISSN: 2186-7976

  184. 放線菌の生産するプレニルカルバゾール類縁体の生合成研究

    小林正弥, 尾崎太郎, 新家一男, 西山真, 葛山智久

    日本農芸化学会関東支部講演要旨集 2013 (Nov) 2013

  185. 放線菌の生産するプレニルカルバゾール類縁体の生合成研究

    小林正弥, 尾崎太郎, 新家一男, 西山真, 葛山智久

    イソプレノイド研究会例会講演要旨集 23rd 2013

  186. オーラシンアルカロイドに抗菌活性を付与するシトクロムP450

    安武義晃, 北川航, 西岡大樹, 尾崎太郎, 西山真, 葛山智久, 田村具博

    日本農芸化学会大会講演要旨集(Web) 2012 3B19A09 (WEB ONLY) 2012/03/05

    ISSN: 2186-7976

  187. Lavanducyanin生合成におけるN-プレニル化酵素の同定

    尾崎太郎, 葛山智久, 西山真

    日本農芸化学会大会講演要旨集(Web) 2012 2012

    ISSN: 2186-7976

  188. 放線菌の生産するラバンデュリル化フェナジンの生合成研究

    尾崎太郎, 葛山智久, 西山真

    日本農芸化学会大会講演要旨集 2011 2011

  189. 放線菌由来ABBAプレニル基転移酵素の機能解析

    尾崎太郎, 西山真, 葛山智久

    日本放線菌学会大会講演要旨集 26th 2011

  190. Streptomyces coelicolor A3(2)由来インドールプレニル基転移酵素の機能解析

    尾崎太郎, 葛山智久, 西山真

    日本農芸化学会大会講演要旨集 2010 2010

  191. 放線菌由来インドールプレニル基転移酵素の機能解析

    尾崎太郎, 西山真, 葛山智久

    ドリコールおよびイソプレノイド研究会例会講演要旨集 20th 2010

  192. Streptomyces coelicolor A3(2)由来SCO7467の機能解析

    尾崎太郎, 葛山智久, 西山真

    日本農芸化学会大会講演要旨集 2009 2009

  193. 芳香族基質プレニル基転移酵素NovQの基質特異性と位置選択性に関する研究

    尾崎太郎, 西山真, 葛山智久

    日本農芸化学会大会講演要旨集 2008 2008

Show all ︎Show first 5

Books and Other Publications 1

  1. 酵母菌・麹菌・乳酸菌の産業応用展開

    南 篤志, 劉 成偉, 尾﨑太郎, 及川英秋

    シーエムシー出版 2018/01

Research Projects 11

  1. アマトキシンの構造多様化機構の解明と構造展開への応用

    尾崎 太郎

    Offer Organization: 日本学術振興会

    System: 科学研究費助成事業

    Category: 基盤研究(B)

    Institution: 東北大学

    2024/04/01 - 2028/03/31

  2. 糸状菌由来新規酸化酵素ファミリーの機能開拓

    尾崎 太郎

    Offer Organization: 日本学術振興会

    System: 科学研究費助成事業 学術変革領域研究(A)

    Category: 学術変革領域研究(A)

    Institution: 東北大学

    2023/04/01 - 2025/03/31

  3. ゲノムマイニングによる糸状菌由来ペプチド系天然物の開拓

    尾崎 太郎

    Offer Organization: 日本学術振興会

    System: 科学研究費助成事業 挑戦的研究(萌芽)

    Category: 挑戦的研究(萌芽)

    Institution: 東北大学

    2022/06/30 - 2025/03/31

  4. Exploring new biologically active metabolites using unidentified gene clusters from Basidiomycota genomes

    Hideaki Oikawa

    Offer Organization: Japan Society for the Promotion of Science

    System: Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (B)

    Category: Grant-in-Aid for Scientific Research (B)

    Institution: Hokkaido University

    2019/04/01 - 2022/03/31

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    To develop the versatile methodology for genome mining of mushroom metabolites, we examined the production of terpenes using genomic DNA sequences. In this report, we initially identified high expression loci (hot spots) in Aspergillus oryzae by sequencing the genomic DNAs from highly yielding transformants which were obtained in our previous biosynthetic studies. Genome editing knock-in of all biosynthetic genes directly to the hot spot showed that A. oryzae correctly spliced more than 90% of the introns in the mushroom genomic DNA gene sequences. Then, we reconstituted two biosynthetic gene clusters using multiple rounds of knock-in of the cDNAs and newly developed repeatable genetic engineering by plasmid recycling. At 100% transformation rate, we obtained a transformant that produced bioactive terpenoids such as nerve growth- factor synthesis activator erinacine antitumor agent melleolides and other fungal metabolites.

  5. Studies on the biosyntheses of fungal dimeric anhydrides

    Ozaki Taro

    Offer Organization: Japan Society for the Promotion of Science

    System: Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (C)

    Category: Grant-in-Aid for Scientific Research (C)

    Institution: Hokkaido University

    2019/04/01 - 2022/03/31

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    In this study, the biosynthetic pathway of fungal dimeric anhydrides such as an antifungal agent zopfiellin were analyzed. As reported in previous studies, maleic anhyride monomers are constructed by the action of polyketide synthase, alkylcitrate synthase, alkylcitrate dehydratase. After the biogenesis of monomers, ketosteroid isomerase-like enzymes (KIs) catalyze dimerization, yielding maleic anhydride dimers. KI in each pathway catalyzes dimerization in distinct mode, showing that KIs are key enzymes for structural diversification of fungal maleic anhydrides. Non-heme iron/alpha-ketoglutarate dependent dioxygenases are also involved in the late stage modifications, further diversifying the structure to furnish structures of natural products.

  6. 植物病原菌が生産するペプチド系化合物の構造多様性創出機構の解析

    尾崎 太郎

    Offer Organization: 日本学術振興会

    System: 科学研究費助成事業 新学術領域研究(研究領域提案型)

    Category: 新学術領域研究(研究領域提案型)

    Institution: 北海道大学

    2019/04/01 - 2021/03/31

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    本研究課題では、糸状菌由来リボソームペプチド (RiPPs) の構造多様性創出機構に焦点をあてている。具体的には、①ホモプシンA (1) などの糸状菌由来RiPPsや②糸状菌由来非リボソームペプチド (NRP) ・シクロクロロチン (2) の生合成研究を行い、これらの化合物の生合成におけるペプチドの修飾機構を解明する。化合物2はNRPに分類されるが、糸状菌由来RiPPsの生合成に関わるDUF3328遺伝子のホモログがペプチドの修飾に関与すると推測し、対象とした。今年度は①、②について研究を行った。 化合物1の生合成については、前年度に確立した生産菌の形質転換法を用いて、生合成遺伝子のノックアウト株を構築した。各形質転換体の代謝産物の解析により、化合物1が有するデヒドロアミノ酸の生合成やチロシン残基のハロゲン化に関わる遺伝子を明らかにした。 また、化合物2についても同様に、生産菌内での標的遺伝子のノックアウトにより機能解析を進めた。生合成遺伝子クラスターに存在する3種のDUF3328遺伝子がそれぞれ、ハロゲン化、分子内アシル基転移、水酸化に関わることを明らかにした。これらの結果は、麹菌を宿主とする異種発現実験の結果からも支持された。 従来、DUF3328遺伝子は糸状菌由来RiPPsの生合成における酸化的環化・水酸化反応に関わることが知られていた。本研究により、DUF3328が上記の反応以外にハロゲン化など多様な機能を持つ酵素を含む一群であることが示唆された。また、DUF3328がNRPの修飾に関わることも示した。これにより、DUF3328がRiPPsだけでなく様々な化合物の修飾に関与することが示唆された。

  7. 麹菌異種発現系を用いた感染時特異的な糸状菌代謝産物の安定供給 Competitive

    尾崎太郎

    Offer Organization: 文部科学省

    System: 科学研究費補助金(新学術領域研究(研究領域提案型)・公募研究)

    Category: 新学術領域研究(研究領域提案型)

    Institution: 北海道大学

    2017/04 - 2019/03

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    本研究課題では、植物病原菌や共生菌において宿主植物感染時に特異的に発現する二次代謝遺伝子に着目した。それらの生合成遺伝子に由来する二次代謝産物は、生産菌からの単離が困難であると考えられる。そこで麹菌を宿主とする生合成遺伝子の異種発現によって、最終産物の同定を試みた。 当初標的の一つとして挙げたTrichoderma virens由来PKS-NRPS遺伝子tex13の機能解析が困難であったことから、前年度は植物病原性糸状菌Pseudocerocospora fijiensisが有するジテルペン生合成遺伝子群の異種発現を行った。それにより宿主への感染時に協調して転写活性化される8遺伝子に由来する新規ブラシッシセン類縁体を同定することができた。また、段階的に異種発現株を構築する過程で複数の生合成中間体を同定し、ブラシッシセン生合成において未解明であった骨格転位を触媒する酵素を明らかにした。本年度は、さらにブラシッシセン生産菌として知られる病原性糸状菌Alternaria brassicicolaにおける生合成遺伝子の機能解析も行った。P. fijiensisとA. brassicolaの生合成遺伝子を比較すると、後者の菌の方が多くの修飾酵素を有している。それらの一つである、P450遺伝子をP. fijiensis由来の遺伝子と共発現したところ、新たな酸化生成物が確認できた。この化合物については、単離・構造解析を行い、13位炭素が水酸化されたことを確認している。今回得られた結果とP. fijiensis由来遺伝子の解析結果を合わせて考えると、現在報告されているほぼすべてのブラシッシセン類縁体の生合成経路を説明可能である。以上、麹菌を宿主とする異種発現によって2種の病原性糸状菌が生産するブラシッシセンの生合成経路を再構築し、その構造多様化機構を明らかにすることができた。

  8. 糸状菌リボソームペプチドの生合成に普遍的な新規環化酵素の機能解明 Competitive

    尾崎太郎

    Offer Organization: 文部科学省

    System: 科学研究費補助金(若手研究(B))

    2017/04 - 2019/03

  9. Studies on the mechanism of action of goadsporin and generation of new derivatives Competitive

    Ozaki Taro

    Offer Organization: Japan Society for the Promotion of Science

    System: Grants-in-Aid for Scientific Research

    Category: Grant-in-Aid for Young Scientists (B)

    Institution: The University of Tokyo

    2014 - 2015

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    Goadsporin is a secondary metabolite produced by Streptomyces sp. TP-A0584, which shows antibiotic activity against actinomycetes. Goadsporin is also known as an inducer of morphogenesis and secondary metabolism in actinomycetes. Previously, it was suggested that goadsporin targeted Ffh, which is an unprecedented target of antibiotics. However, the details of the mechanism of action remains to be elucidated. In this study, to reveal the mechanism of action of goadsporin, crystallization of Ffh was examined. Biochemical assays, including pull-down assay and surface plasmon resonance, were also performed to analyze the interaction between Ffh and goadsporin. As a result, goadsporin showed interaction with Ffh in both assays. These results suggested that the molecular target of goadsporin was Ffh.

  10. Studies on the mechanism for goadsporin resistance Competitive

    Taro OZAKI

    Offer Organization: Ministry of Education, Culture, Sports, Science and Technology

    System: Grants-in-Aid for Scientific Research(研究活動スタート支援)

    Category: 研究活動スタート支援

    Institution: 東京大学

    2013 - 2013

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    Goadsporin is an antibiotic which inhibits the growth of actinomycetes. As the molecular target of goadsporin was proposed to be unprecedented, it was expected that the characterization of the mechanism of goadsporin action would lead to the development of drugs which possessed novel mechanism of action. This study aimed to reveal the mechanism of goadsporin action. Ffh, a possible target of goadsporin was successfully expressed as a soluble protein in Escherichia coli. GodI, a goadsporin-resistant Ffh homologue was also obtained as a recombinant protein. Using recombinant Ffh and GodI, crystallization experiments were performed. As a result, microcrystal-like objects were obtained in some conditions.

  11. 新規プレニル基転移酵素の機能解析と有用化合物創製への応用

    尾崎 太郎

    Offer Organization: 日本学術振興会

    System: 科学研究費助成事業 特別研究員奨励費

    Category: 特別研究員奨励費

    Institution: 東京大学

    2010 - 2012

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    本年度は前年度同定したシクロラバンデュリルジリン酸合成酵素(CLDS)の組換えタンパク質をDMAPPと反応し、その反応産物の構造解析を行った。フォスファターゼによって反応産物からジリン酸を除去した化合物の構造をN厭によって解析したところ、シクロラバンデュロールであることが確かめられた。そのことより、CLDSがDMAPPの縮合と環化によってシクロラバンデュリルジリン酸を合成する新規のプレニルジリン酸合成酵素であることが明らかになった。このCLDSによって合成したシクロラバンデュリルジリン酸を、前年度までに同定したプレニル基転移酵素とフラビン依存型酸化酵素の反応系に供給して、フェナジン-1-カルボン酸のプレニル化反応を行った。この反応によるラバンドシアニンの生成が確認できたことから、シクロラバンデュリルジリン酸がプレニル基供与体として働くことも明らかにすることができた。また、ラバンドシアニンの生産菌においてclds遺伝子を欠失させたところ、ラバンドシアニンの生産が失われたため、CLDSがラバンドシアニンの生合成において確かにシクロラバンデュリ'ル基の形成に関与することが確かめられた。さらに、本来ラバンドシアニンを生産しない放線菌Streptomyces lividans TK23を用いたラバンドジアニン異種生産系を構築し、本研究で同定した遺伝子がラバンドシアニンの生合成に必要十分であることを確かめた。CLDSの詳細な反応機構を明らかにするために結晶構造解析も試みた。最終的な構造の決定には至らなかったが、Nativeタンパク質、およびセレノメチオニン置換体タンパク質の結晶を作製し、高い分解能の回折データを取得することができた。今後、構造を明らかにすることで新規のテルペノイド生合成機構が明らかになると期待される。以上のラバンドシアニンの生合成研究に加えて、放線菌の生産するプレニル化インドールの生合成についても研究を行った。

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