Heterologous Production of Fungal Maleidrides Reveals the Cryptic Cyclization Involved in their Biosynthesis |
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| Authors: | 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 Prof Russell J Cox |
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| Institution: | 1. Institute for Organic Chemistry, Leibniz University of Hannover, Germany;2. School of Chemistry, University of Bristol, Bristol, UK;3. Syngenta, Bracknell, Berkshire, UK;4. School of Biological Sciences, Bristol Life Sciences Building, University of Bristol, Bristol, UK |
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| 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. |
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| Keywords: | biosynthesis cyclization enzymes maleidride polyketides |
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