Development of a rational protocol searching novel biosynthetic gene clusters for natural product synthesis

2014 Fiscal Year Final Research Report

• Project/Area Number: 25560398
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Biomolecular chemistry
• Research Institution: Hokkaido University
• Principal Investigator: OIKAWA Hideaki 北海道大学, 理学(系)研究科(研究院), 教授 (00185175)
• Co-Investigator(Renkei-kenkyūsha): ISHIKAWA Jun 国立感染症研究所, 生物活性物質部, 室長 (40202957) ; MINAMI Atsushi 北海道大学, 大学院理学研究院, 助教 (40507191)
• Project Period (FY): 2013-04-01 – 2015-03-31
• Keywords: 生合成 / 天然物 / ゲノム情報 / 物質生産 / 糸状菌 / 酸無水物

Outline of Final Research Achievements

To identify novel type-gene clusters of natural products in fungal genome, we chose the fungal dimeric anhydrides zopfiellin and phomoidride. Draft genome sequences of two anhydride producing fungi allowed us to identify three enzyme genes that were commonly located in two individual clusters. Heterologous expression of three genes responsible for the phomoidride monomer synthesis in Aspergillus oryzae has successfully provided phomoidride monomer derivative. In addition, the enzymatic reactions of two recombinant enzymes gave the corresponding monomers. The anhydrides from the enzymatic reactions were identical to the synthetic monomers, thus confirming their structures. Based on these results, we have developed the method identifying novel gene cluster for the biosynthesis of alkylcitrate natural products.

Free Research Field

生物有機化学