Enzyme engineering for natural product biosynthesis

2014 Fiscal Year Final Research Report

• Project/Area Number: 23241068
• Research Category: Grant-in-Aid for Scientific Research (A)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Living organism molecular science
• Research Institution: The University of Tokyo
• Principal Investigator: ABE IKURO 東京大学, 薬学研究科(研究院), 教授 (40305496)
• Co-Investigator(Kenkyū-buntansha): WAKIMOTO Toshiyuki 東京大学, 大学院薬学系研究科, 准教授 (70363900) ; AWAKAWA Takayoshi 東京大学, 大学院薬学系研究科, 助教 (80609834) ; MATSUDA Yudai 東京大学, 大学院薬学系研究科, 助教 (10720766) ; MORITA Hiroyuki 東京大学, 大学院薬学系研究科, 助教 (20416663)
• Co-Investigator(Renkei-kenkyūsha): SUGIO Shigetoshi 三菱化学, バイオ技術研究所, 主幹研究員 (10537343) ; NOGUCHI Hiroshi 静岡県立大学, 薬学部, 教授 (60126141) ; KUSHIRO Testuo 明治大学, 農学部, 准教授 (80373299)
• Project Period (FY): 2011-04-01 – 2015-03-31
• Keywords: 生合成 / 二次代謝酵素 / 機能制御 / 物質生産 / 酵素工学

Outline of Final Research Achievements

Several enzymes involved in the biosynthesis of natural products, such as plant polyketide synthase and CoA-ligase, exhibit remarkable catalytic versatility and substrate promiscuity. This makes the enzymes an excellent platform for enzyme engineering and further production of structurally divergent molecules. In this study, on the basis of the X-ray crystal structures of the enzymes, we succeeded in production of chemically and structurally divergent unnatural natural products, by structure-based enzyme engineering and precursor directed biosynthesis. In addition, we succeeded in elucidation of biosynthetic machinery of complex natural products including calyculin, teleocidin, and antimycin.

Free Research Field

天然物化学、生物有機化学