Details:

Alternative Title:
J Am Chem Soc
Personal Author:
Mao, Xu-Ming ; Zhan, Zha-Jun ; Grayson, Matthew N. ; Tang, Man-Cheng ; Xu, Wei ; ... More +
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 Less -
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:
[+]
Article 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/
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/ Less -
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:

Supporting Files

• 	nihms793053f4.gif	gif
  	nihms793053f4.jpg	jpeg
  	nihms793053f5.jpg	jpeg
  	NIHMS793053-supplement-SI.pdf	pdf
  	nihms793053.nxml	xml
  	nihms793053f1.gif	gif
  	nihms793053f1.jpg	jpeg
  	nihms793053f2.gif	gif
  	nihms793053f2.jpg	jpeg
  	nihms793053f3.gif	gif
  	nihms793053f3.jpg	jpeg

More +