2020 Fiscal Year Final Research Report
Mechanistic Analysis of Biosynthetic Machinery for Rational Redesign of Microbial Secondary Metabolites
| Project Area | Creation of Complex Functional Molecules by Rational Redesign of Biosynthetic Machineries |
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| Project/Area Number |
16H06451
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| Research Category |
Grant-in-Aid for Scientific Research on Innovative Areas (Research in a proposed research area)
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| Allocation Type | Single-year Grants |
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| Review Section |
Science and Engineering
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| Research Institution | Tokyo Institute of Technology |
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Principal Investigator |
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| Project Period (FY) |
2016-06-30 – 2021-03-31
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| Keywords | 生合成 / 二次代謝物 / リデザイン / 酵素 / 遺伝子 |
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| Outline of Final Research Achievements |
In this study, we analyzed the functions of aminoglycoside, macrolactam, and fosfomycin biosynthetic enzymes. In the aminoglycoside antibiotics, we demonstrated that the biosynthesis of the aminoglycoside antibiotic kanamycin proceeds stepwise. In macrolactam antibiotics, we are the first to elucidate protein-protein interactions between the acyl carrier protein of polyketide synthase and other domains by using a covalent bond-forming probe. Furthermore, based on this information, we succeeded in obtaining analogs of incednin and hitachimycin belonging to macrolactam antibiotics. In addition, we were able to clarify the biosynthetic pathway of fosfomycin in streptomyces.
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| Free Research Field |
天然物化学
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| Academic Significance and Societal Importance of the Research Achievements |
本研究では、その対象をさまざまな微生物に由来する特徴ある化学構造と有用な生理活性を持つアミノグリコシド系抗生物質およびポリケチド系抗生物質の生合成系を中心にして、酵素タンパク質・分子反応機構を座標軸として、特徴ある二次代謝反応系について有機化学、構造生物学と分子生物学を融合して微生物二次代謝生合成系の精密機能解析に基づいた非天然型天然物の生合成リデザインを指向し、新しい学術の開拓を目的としてきた。その結果、タンパク質間相互作用解析の手法を新たに示すなど、学術的に大きな成果をもたらした。また、類縁体創製の面でも成果を挙げており、新たな薬剤開発などに多大な影響を与えることが期待される。
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