Tandem Prenyltransferases Catalyze Isoprenoid Elongation and Complexity Generation in Biosynthesis of Quinolone Alkaloids

Details

• Alternative Title:
  J Am Chem Soc
• Personal Author:
  Zou, Yi ; Zhan, Zhajun ; Li, Dehai ; Tang, Mancheng ; Watanabe, Kenji ; Tang, Yi
• 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.
• Subjects:
  Alkaloids Article Biocatalysis Dimethylallyltranstransferase Molecular Structure Penicillium Quinolones Terpenes
• Source:
  J Am Chem Soc. 137(15):4980-4983
• Pubmed ID:
  25859931
• Pubmed Central ID:
  PMC4610815
• Document Type:
  Journal Article
• Funding:
  DP1 GM106413/GM/NIGMS NIH HHSUnited States/ ; R56 AI101141/AI/NIAID NIH HHSUnited States/ ; 1DP1GM106413/DP/NCCDPHP CDC HHSUnited States/ ; 1R56AI101141/AI/NIAID NIH HHSUnited States/
• Volume:
  137
• Issue:
  15
• Collection(s):
  CDC Public Access
• Main Document Checksum:
  urn:sha256:6bda8f430dcaaf76a26c2e932220755f29566dfc5fd71f02c6321d0434572d1c
• Download URL:
  https://stacks.cdc.gov/view/cdc/35104/cdc_35104_DS1.pdf
• File Type:
  [PDF - 885.92 KB ]