Heterologous Production of Fungal Maleidrides Reveals the Cryptic Cyclization Involved in their Biosynthesis
Article 2016 en
Authors
KW
Katherine Williams
AS
Agnieszka J. Szwalbe
NM
Nicholas P. Mulholland
Abstract
1 min read
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.
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