Engineered biosynthesis based on functional redesign of aromatic prenyltransferases

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K06627
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 47050:Environmental and natural pharmaceutical resources-related
• Research Institution: Iwate Medical University (2023); University of Toyama (2021-2022)
• Principal Investigator: Taura Futoshi 岩手医科大学, 薬学部, 教授 (00301341)
• Co-Investigator(Kenkyū-buntansha): 森田 洋行 富山大学, 学術研究部薬学・和漢系, 教授 (20416663)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: プレニル基転移酵素 / 生合成 / 二次代謝 / 薬用植物

Outline of Final Research Achievements

In this study, I demonstrated that the Cannabis prenyltransferase CsPT4 accepts a wide range of aromatic and prenyl substrates other than the physiological substrates olivetolic acid (OLA) and GPP, and produces a number of prenylated polyphenols, including novel compounds. Furthermore, the enzymatic reaction products were examined for their antiausterity activity against human pancreatic cancer cells. The results proved that the novel O-prenylated chalcone derivatives obtained in this study showed activity comparable to that of arctigenin, an well-studied anti-cancer drug candidate compound. The study also succeeded in identifying a novel O-prenyltransferase FaPT1 from Ferula assa-foetida involved in the biosynthesis of the anticancer candidate compound umbelliprenin.

Free Research Field

天然物化学

Academic Significance and Societal Importance of the Research Achievements

プレニル化天然物は注目すべき生物活性を有するが、生合成酵素の機能研究や物質生産への応用研究はいまだ不十分である。本研究では大麻プレニル基転移酵素が植物酵素としては例外的に多様な基質と反応して、ヒト膵がん細胞に顕著な細胞毒性を示す多数のプレニル化ポリフェノールを合成できることを初めて証明した。本成果は酵素を活用した有用天然物の酵素合成に展開可能であり、学術的ならびに社会的意義が大きい。さらに本研究では抗がん天然物umbellipreninの生合成に関わるアギ由来新規O-プレニル基転移酵素FaPT1を同定することにも成功した。本酵素も広範な基質特異性を有しており、有用物質生産への応用が期待される。