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.
Subjects:
[+]
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 HHSUnited States/ ; 1R01GM085128/GM/NIGMS NIH HHSUnited States/ ; GM-0846/GM/NIGMS NIH HHSUnited States/ ; T32 GM008496/GM/NIGMS NIH HHSUnited States/ ; 1DP1GM106413/DP/NCCDPHP CDC HHSUnited States/ ; ... More +
DP1 GM106413/GM/NIGMS NIH HHSUnited States/ ; 1R01GM085128/GM/NIGMS NIH HHSUnited States/ ; GM-0846/GM/NIGMS NIH HHSUnited States/ ; T32 GM008496/GM/NIGMS NIH HHSUnited States/ ; 1DP1GM106413/DP/NCCDPHP CDC HHSUnited States/ ; R01 GM085128/GM/NIGMS NIH HHSUnited States/ Less -
Collection(s):
CDC Public Access
Main Document Checksum:
[+]
urn:sha256:4d61b7cc9a2e3977abcd168b6a485b30fe35f5d3d3130631cd42d354d4d68cc6
Download URL:
https://stacks.cdc.gov/view/cdc/29812/cdc_29812_DS1.pdf
File Type:

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