Studies on biosynthetic machineries for cyclic terpenoids and nucleoside antibiotics

2014 Fiscal Year Final Research Report

• Project Area: Biosynthetic machinery: Deciphering and regulating the system for bioactive metabolite diversification
• Project/Area Number: 23108101
• Research Category: Grant-in-Aid for Scientific Research on Innovative Areas (Research in a proposed research area)
• Allocation Type: Single-year Grants
• Review Section: Science and Engineering
• Research Institution: Hokkaido University
• Principal Investigator: DAIRI Tohru 北海道大学, 工学(系)研究科(研究院), 教授 (70264679)
• Co-Investigator(Renkei-kenkyūsha): KATO Nobuo 大阪大学, 産業科学研究所, 教授 (50150537) ; SATOH Yasuharu 北海道大学, 大学院工学研究院, 助教 (30360928) ; ARAI Ryouichi 信州大学, ファイバーナノテク国際若手研, 助教 (50344023)
• Project Period (FY): 2011-04-01 – 2015-03-31
• Keywords: 生合成 / インドールジテルペン / 糸状菌 / プレニルトランスフェラーゼ / フタロシン / ペプチドリガーゼ

Outline of Final Research Achievements

1. Fusicoccin A is a diterpene glucoside produced by the fungus Phomopsis amygdali and its derivative lacking the OH group at the 12-position is revealed to be a potential anti-cancer drug. We therefore constructed a mutant producing the desirable intermediate by biosynthetic engineering. 2. Three fungal prenyltransferases, PaxC, PaxD, and AtmD, all of which are responsible for biosynthesis of indole diterpene compounds, were characterized. 3. Aminodeoxyfutalosine is the first intermediate in the new menaquinone biosynthetic pathway. We demonstrated that a radical S-adenosyl methionine enzyme (MqnE) catalyzed the addition of the adenosyl radical to the double bond of 3-[(1-carboxyvinyl)oxy]benzoic acid derived from chorismate by MqnA. 4. During the biosynthetic studies of pheganomycin, we identified a new ATP-grasp enzyme, which phosphorylated the non-proteogenic amino acids with ATP and the successive nucleophilic attack of the peptides.

Free Research Field

生合成工学