Heterologous Production of Fungal Maleidrides Reveals the Cryptic Cyclization Involved in their Biosynthesis. Issue 23 (21st April 2016)

• Record Type: Journal Article
• Authors: Williams, Katherine; Szwalbe, Agnieszka J.; Mulholland, Nicholas P.; Vincent, Jason L.; Bailey, Andrew M.; Willis, Christine L.; Simpson, Thomas J.; Cox, Russell J.
• Is Part Of: Angewandte Chemie international edition. Volume 55:Issue 23(2016)
• Page Start: 6784
• Page End: 6788
• Publication Date: 2016-04-21
• Subjects: biosynthesis -- cyclization -- enzymes -- maleidride -- polyketides; Chemistry -- Periodicals; 540
• DOI: 10.1002/anie.201511882
• Languages: English
• ISSNs: 1433-7851

Abstract

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. Abstract : Ring cycle : The enzymes involved in the cyclization of the maleidride family of bioactive fungal natural products, including agnestadride A and byssochlamic acid, were identified. These previously unknown proteins show homology to ketosteroid isomerases (KI‐like) and phosphatidylethanolamine‐binding proteins (PEBP‐like).