Efficient Biosynthesis of Fungal Polyketides Containing the Dioxabicyclo-octane Ring System

Details

• Alternative Title:
  J Am Chem Soc
• Personal Author:
  Mao, Xu-Ming ; Zhan, Zha-Jun ; Grayson, Matthew N. ; Tang, Man-Cheng ; Xu, Wei ; Li, Yong-Quan ; Yin, Wen-Bing ; Lin, Hsiao-Ching ; Chooi, Yit-Heng ; Houk, K. N. ; Tang, Yi
• Description:
  Aurovertins are fungal polyketides that exhibit potent inhibition of adenosine triphosphate synthase. Aurovertins contain a 2,6-dioxabicyclo[3.2.1]octane ring that is proposed to be derived from a polyene precursor through regioselective oxidations and epoxide openings. In this study, we identified only four enzymes required to produce aurovertin E. The core polyketide synthase produces a polyene α-pyrone. Following pyrone O-methylation by a methyltransferase, a flavin-dependent mono-oxygenase and an epoxide hydrolase can iteratively transform the terminal triene portion of the precursor into the dioxabicyclo[3.2.1]octane scaffold. We demonstrate that a tetrahydrofuranyl polyene is the first stable intermediate in the transformation, which can undergo epoxidation and anti-Baldwin 6-endo-tet ring opening to yield the cyclic ether product. Our results further demonstrate the highly concise and efficient ways in which fungal biosynthetic pathways can generate complex natural product scaffolds.
• Subjects:
  Aurovertins Fungi Octanes Polyketides Stereoisomerism
• Source:
  J Am Chem Soc. 137(37):11904-11907
• Pubmed ID:
  26340065
• Pubmed Central ID:
  PMC4903023
• Document Type:
  Journal Article
• Funding:
  DP1 GM106413/GM/NIGMS NIH HHSUnited States/ ; R01 GM085128/GM/NIGMS NIH HHSUnited States/ ; 1DP1GM106413/DP/NCCDPHP CDC HHSUnited States/ ; 1R01GM085128/GM/NIGMS NIH HHSUnited States/
• Volume:
  137
• Issue:
  37
• Collection(s):
  CDC Public Access
• Main Document Checksum:
  urn:sha256:a0da26604f42c21f299143275676332f2a2791155bdcb15b0c8777d1d05c4010
• Download URL:
  https://stacks.cdc.gov/view/cdc/39865/cdc_39865_DS1.pdf
• File Type:
  [PDF - 976.19 KB ]