Heterologous Production of Fungal Maleidrides Reveals the Cryptic Cyclization Involved in their Biosynthesis
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- 作者：Dr. Katherine Williams ; Agnieszka J. Szwalbe ; Dr. Nicholas P. Mulholland ; Dr. Jason L. Vincent ; Dr. Andrew M. Bailey ; Prof. Christine L. Willis ; Prof. Thomas J. Simpson and Prof. Russell J. Cox
- 刊名：Angewandte Chemie International Edition
- 出版年：2016
- 出版时间：June 1, 2016
- 年：2016
- 卷：55
- 期：23
- 页码：6784-6788
- 全文大小：1291K
- ISSN：1521-3773
文摘
Fungal maleidrides are an important family of bioactive secondary metabolites that consist of 7, 8, or 9-membered carbocycles with one or two fused maleic anhydride moieties. The biosynthesis of byssochlamic acid (a nonadride) and agnestadride A (a heptadride) was investigated through gene disruption and heterologous expression experiments. The results reveal that the precursors for cyclization are formed by an iterative highly reducing fungal polyketide synthase supported by a hydrolase, together with two citrate-processing enzymes. The enigmatic ring formation is catalyzed by two proteins with homology to ketosteroid isomerases, and assisted by two proteins with homology to phosphatidylethanolamine-binding proteins.