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Tandem Prenyltransferases Catalyze Isoprenoid Elongation and Complexity Generation in Biosynthesis of Quinolone Alkaloids
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4 22 2015
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Source: J Am Chem Soc. 137(15):4980-4983
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Alternative Title:J Am Chem Soc
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Description:Modification of natural products with prenyl groups and the ensuing oxidative transformations are important for introducing structural complexity and biological activities. Penigequinolones (1) are potent insecticidal alkaloids that contain a highly modified 10-carbon prenyl group. Here we reveal an iterative prenylation mechanism for installing the 10-carbon unit using two aromatic prenyltransferases (PenI and PenG) present in the gene cluster of 1 from Penicillium thymicola. The initial Friedel-Crafts alkylation is catalyzed by PenI to yield dimethylallyl quinolone 6. The five-carbon side chain is then dehydrogenated by a flavin-dependent monooxygenase to give aryl diene 9, which serves as the electron-rich substrate for a second alkylation with dimethylallyl diphosphate to yield stryrenyl product 10. The completed, oxidized 10-carbon prenyl group then undergoes further structural morphing to yield yaequinolone C (12), the immediate precursor of 1. Our studies have therefore uncovered an unprecedented prenyl chain extension mechanism in natural product biosynthesis.
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Pubmed ID:25859931
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Pubmed Central ID:PMC4610815
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Volume:137
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Issue:15
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