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2020 Fiscal Year Final Research Report

Comprehensive metabolic analysis of a model host for secondary metabolite production

Planned Research

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Project AreaCreation of Complex Functional Molecules by Rational Redesign of Biosynthetic Machineries
Project/Area Number 16H06447
Research Category

Grant-in-Aid for Scientific Research on Innovative Areas (Research in a proposed research area)

Allocation TypeSingle-year Grants
Review Section Science and Engineering
Research InstitutionKitasato University

Principal Investigator

Ikeda Haruo  北里大学, 感染制御科学府, 特任教授 (90159632)

Co-Investigator(Kenkyū-buntansha) 小松 護  北里大学, 感染制御科学府, 講師 (40414057)
Project Period (FY) 2016-06-30 – 2021-03-31
Keywords応用微生物 / ゲノム / 抗生物質 / 発現制御 / バイオテクノロジー
Outline of Final Research Achievements

Several deletion mutants are required for evaluation of oricess in the biosynthesis of secondary metabolites and analysis of metabolism involved in supply of precursors in streptomtcetes. We have developed an excelent methods for construction of deletion mutants in Streptomyces. A comprehensive analysis of post-translational modification of modular polyketide synthases and non-ribosomal peptide synthetases could be perormed using our genome-minimized versatile host strain. On the other hand, we studied the metabolic analysis of the primary metabolism during secondary metabolite production. The production of chloramphenicol could be improved by increaased flux of pentose-phosphate pathway. It also gave a new finding that the regulatory gene in the biosynthetic gene cluster can control the expression of the different biosynthetic genes.

Free Research Field

微生物分子遺伝学

Academic Significance and Societal Importance of the Research Achievements

放線菌における遺伝子改変に関する最適な方法は現在まで確立はされていなかった。本研究では多数の欠失変異株の取得などの迅速かつ簡便な、そしてStreptomyces属の多くの菌種にも適用できる方法を開発できたことは大いに意義のあることである。また、これまでI型ポリケチド合成酵素や非リボソーム型ペプチド合成酵素の翻訳後修飾に関しての特異性などの解析はこれらの酵素の扱いができなかったため全く不明であった。この問題点は我々の異種発現系を利用することで物質生産という形質で評価することのできる画期的な方法を開発することができた。そして多くの上記合成酵素を修飾可能な酵素を見出すことができたことは有用である。

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Published: 2022-01-27  

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