The Biosynthesis and Catabolism of the Maleic Anhydride Moiety of Stipitatonic Acid

• Published in: Angewandte Chemie (International ed.) Vol. 53; no. 29; pp. 7519 - 7523
• Main Authors: al Fahad, Ahmed, Abood, Amira, Simpson, Thomas J., Cox, Russell J.
• Format: Journal Article
• Language: English
• Published: Weinheim WILEY-VCH Verlag 14.07.2014; WILEY‐VCH Verlag; Wiley Subscription Services, Inc
• Edition: International ed. in English
• Subjects: Aldehydes; Assaying; Biosynthesis; Carbon; Chromatography, High Pressure Liquid; Construction; Decarboxylation; Fungi; Maleic anhydride; Maleic Anhydrides - chemistry; Pathways; Tropolone - analogs & derivatives; Tropolone - chemistry; Tropolone - metabolism; tropolones; maleic anhydride; tropolones; fungi; biosynthesis
• ISSN: 1433-7851; 1521-3773
• DOI: 10.1002/anie.201403450

A series of directed knockout experiments, combined with an in vitro assay of pathway components, has elucidated for the first time the chemical steps involved in the biosynthesis of the tropolone class of fungal maleic anhydrides. The pathway involves the stepwise oxidation of aldehyde and methyl carbon atoms to form a 1,2‐dicarboxylate. A hydrolase‐catalyzed interconversion of this and the corresponding maleic anhydride, followed by decarboxylation of the diacid leads to the pathway’s final product of stipitatic acid. Building and demolition: The biochemical steps leading from the first‐formed tropolone of the stipitatic acid pathway in the fungus Talaromyces stipitatus via the maleic anhydride containing stipitatonic acid have been determined by coordinated gene knockout and in vitro assays. The formation of shunt products including cordytropolone and talaroditropolone sheds light on the metabolism in other fungal organisms.