Horizontal gene transfer based discovery of biosynthetic genes of natural products from marine sponges

2023 Fiscal Year Final Research Report

• Project/Area Number: 22K20717
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Multi-year Fund
• Review Section: 0801:Pharmaceutical sciences and related fields
• Research Institution: University of the Ryukyus
• Principal Investigator: Jomori Takahiro 琉球大学, 理学部, 助教 (60964898)
• Project Period (FY): 2022-08-31 – 2024-03-31
• Keywords: 海綿動物 / 生合成遺伝子 / 海洋天然物 / 生合成 / 修飾酵素 / メタゲノム / メンブレンベシクル / 水平伝播

Outline of Final Research Achievements

Marine sponges are well-known bioresources for bioactive substances such as anticancer agents but supply problems are still solved. In this research project, we attempted to acquire biosynthetic genes, which serve as blueprints for natural products from sponges, to get insights into the solution to the supply problem. Since genes responsible for horizontal transfer have been encoded in biosynthetic gene clusters so far, we fractionated membrane vesicles, important for horizontal transfer, and obtained metagenomic DNA sequences by a nanopore sequencer. From the obtained DNA information, we successfully found a putative biosynthetic gene cluster for the antifungal agent using the analysis software AntiSMASH. In the future, we will explore the application of biocatalysts through the functional analysis of modification enzymes.

Free Research Field

天然物化学

Academic Significance and Societal Importance of the Research Achievements

海綿由来の生合成遺伝子の探索は共生微生物を含むすべての海綿組織メタゲノムDNAから見出すか、微生物のシングルセル分析と遺伝子増幅を駆使して数例報告されてきた。一方、この常法が通用しないのが大多数の海綿を占める。本成果では、海綿のメンブレンベシクルDNAを用いることで生合成遺伝子を濃縮することで結果的に生合成遺伝子の発見へとつながったことが示唆され、今後他の海綿からの生合成遺伝子探索の開拓基盤となることが期待される。天然物の設計図である生合成遺伝子クラスターを見出すことが可能となれば、新奇な修飾を基盤に生体触媒開発や、異種宿主発現株の構築、稀少天然物の量的供給への基盤構築へとつながる。