Heterologous production of fungal maleidrides reveals the cryptic cyclization involved in their biosynthesis

Williams, Katherine; Szwalbe, Agnieszka J; Mulholland, Nicholas P; Vincent, Jason L; Bailey, Andy; Willis, Christine L; Simpson, Thomas J; Cox, Russell J

Abstract

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.

• Journal Article Type: Article
• Online Publication Date: Apr 21, 2016
• Publication Date: Jun 1, 2016
• Deposit Date: Apr 11, 2024
• Publicly Available Date: Apr 12, 2024
• Journal: Angewandte Chemie - International Edition
• Print ISSN: 1433-7851
• Electronic ISSN: 1521-3773
• Publisher: Wiley
• Peer Reviewed: Peer Reviewed
• Volume: 55
• Issue: 23
• Pages: 6784-6788
• DOI: https://doi.org/10.1002/anie.201511882
• Keywords: biosynthesis, cyclization, enzymes, maleidride, polyketides
• Public URL: https://uwe-repository.worktribe.com/output/11881333
• Publisher URL: http://dx.doi.org/10.1002/anie.201511882