Details:

Alternative Title:
J Am Chem Soc
Publisher's site:
http://dx.doi.org/10.1021/ja408966t
Personal Author:
Chooi, Yit-Heng ; Hong, Young J. ; Cacho, Ralph A. ; Tantillo, Dean J. ; Tang, Yi
Chooi, Yit-Heng ; Hong, Young J. ; Cacho, Ralph A. ; Tantillo, Dean J. ; Tang, Yi Less -
Description:
Viridicatumtoxin (1) is a tetracycline-like fungal meroterpenoid with a unique, fused spirobicyclic ring system. Puzzlingly, no dedicated terpene cyclase is found in the gene cluster identified in Penicillium aethiopicum. Cytochrome P450 enzymes VrtE and VrtK in the vrt gene cluster were shown to catalyze C5-hydroxylation and spirobicyclic ring formation, respectively. Feeding acyclic previridicatumtoxin to Saccharomyces cerevisiae expressing VrtK confirmed that VrtK is the sole enzyme required for cyclizing the geranyl moiety. Thus, VrtK is the first example of a P450 that can catalyze terpene cyclization, most likely via initial oxidation of C17 to an allylic carbocation. Quantum chemical modeling revealed a possible new tertiary carbocation intermediate E that forms after allylic carbocation formation. Intermediate E can readily undergo concerted 1,2-alkyl shift/1,3-hydride shift, either spontaneously or further aided by VrtK, followed by C7 Friedel-Crafts alkylation to afford 1. The most likely stereochemical course of the reaction was proposed on the basis of the results of our computations.
Subject:
[+]
Article
Cyclization
Cytochrome P-450 Enzyme System
Gene Deletion
Gene Expression
Hydroxylation
Models, Molecular
Multigene Family
Mycotoxins
Penicillium
Saccharomyces Cerevisiae
Terpenes

Source:
J Am Chem Soc. 135(45):16805-16808.
Pubmed ID:
24161266
Pubmed Central ID:
PMC3872057
Document Type:
Journal Article
Funding:
DP1 GM106413/GM/NIGMS NIH HHS/United States ; 1R01GM085128/GM/NIGMS NIH HHS/United States ; GM-0846/GM/NIGMS NIH HHS/United States ; T32 GM008496/GM/NIGMS NIH HHS/United States ; 1DP1GM106413/DP/NCCDPHP CDC HHS/United States ; ... More +
DP1 GM106413/GM/NIGMS NIH HHS/United States ; 1R01GM085128/GM/NIGMS NIH HHS/United States ; GM-0846/GM/NIGMS NIH HHS/United States ; T32 GM008496/GM/NIGMS NIH HHS/United States ; 1DP1GM106413/DP/NCCDPHP CDC HHS/United States ; R01 GM085128/GM/NIGMS NIH HHS/United States Less -
Collection(s):
CDC Public Access
Main Document Checksum:
[+]
urn:sha256:4d61b7cc9a2e3977abcd168b6a485b30fe35f5d3d3130631cd42d354d4d68cc6
File Type:

Supporting Files

• 	nihms-537034-f0005.gif	gif
  	nihms-537034-f0005.jpg	jpeg
  	nihms-537034-f0006.gif	gif
  	nihms-537034-f0006.jpg	jpeg
  	nihms-537034-f0007.gif	gif
  	nihms-537034-f0007.jpg	jpeg
  	nihms-537034.nxml	xml
  	NIHMS537034-supplement-1_si_001.pdf	pdf
  	nihms-537034-f0001.gif	gif
  	nihms-537034-f0001.jpg	jpeg
  	nihms-537034-f0002.gif	gif
  	nihms-537034-f0002.jpg	jpeg
  	nihms-537034-f0003.gif	gif
  	nihms-537034-f0003.jpg	jpeg
  	nihms-537034-f0004.gif	gif
  	nihms-537034-f0004.jpg	jpeg

More +