Development of Heterogeneous Production Technology for Useful Natural Compounds from Difficult-to-Cultivate Microorganisms by Semi-Artificial Gene Clusters

2022 Fiscal Year Final Research Report

• Project/Area Number: 21K14798
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 38040:Bioorganic chemistry-related
• Research Institution: National Institute of Advanced Industrial Science and Technology
• Principal Investigator: Kudo Kei 国立研究開発法人産業技術総合研究所, 生命工学領域, 研究員 (80828161)
• Project Period (FY): 2021-04-01 – 2023-03-31
• Keywords: 天然物化学 / 異種発現 / 海洋天然物 / 生合成 / 医薬品 / 物質生産 / Pseudomonas

Outline of Final Research Achievements

We aimed to construct a semi-artificial biosynthetic gene cluster to produce compounds produced by difficult-to-cultivate marine microorganisms in culturable bacteria from another genus. Using the safracin biosynthetic gene cluster, which has already been shown to function in the host microorganism, as a template, we constructed five types of vectors containing 21 genes from 16 putative orthologs. These were introduced into the host, Pseudomonas putida, in six different combinations, but the production of the expected compounds was not observed. As future work, it is necessary to carry out basic research, such as determining expression bottlenecks and strictly selecting codon optimization algorithms to utilize genetic resources that have been difficult to use.

Free Research Field

天然物化学

Academic Significance and Societal Importance of the Research Achievements

本研究では、カイメン由来のtetrahydroisoquinoline化合物であるrenieramycin類の生合成遺伝子を題材として、Pseudomonas putidaでの異種発現生産を目指した。目的物質の生産には至らなかったものの、より詳細な解析を行う材料となる菌株を構築することができた。今後異種生産が達成されれば、ecteinascidin-743など様々な難培養微生物由来の有用天然化合物の発酵生産へと結びつけることができる。