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Cyclization of a Cellular Dipentaenone by Streptomyces coelicolor Cytochrome P450 154A1 without Oxidation/Reduction

Q Cheng, DC Lamb, Steven Kelly Orcid Logo, L Lei, FP Guenguerich, Diane Kelly

Journal of the American Chemical Society, Volume: 132, Issue: 43, Pages: 15173 - 15175

Swansea University Authors: Steven Kelly Orcid Logo, Diane Kelly

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DOI (Published version): 10.1021/ja107801v

Abstract

We report a comprehensive genetic, metabolomic, and biochemical study on the catalytic properties of Streptomyces coelicolor cytochrome P450 (P450) 154A1, known to have a unique heme orientation in its crystal structure. Deletion of the P450 154A1 gene compromised the long-term stability of the bact...

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Published in: Journal of the American Chemical Society
ISSN: 0002-7863 1520-5126
Published: 1155 16TH ST, NW, WASHINGTON, DC 20036 USA AMER CHEMICAL SOC 2010
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URI: https://cronfa.swan.ac.uk/Record/cronfa9901
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Abstract: We report a comprehensive genetic, metabolomic, and biochemical study on the catalytic properties of Streptomyces coelicolor cytochrome P450 (P450) 154A1, known to have a unique heme orientation in its crystal structure. Deletion of the P450 154A1 gene compromised the long-term stability of the bacterial spores. A novel dipentaenone (1) with a high degree of conjugation was identified as an endogenous substrate of P450 154A1 using a metabolomics approach. The biotransformation of 1 by P450 154A1 was shown to be an unexpected intramolecular cyclization to a Paterno-Buchi-like product, without oxidation/reduction
Keywords: DRUG DISCOVERY; A3(2); IDENTIFICATION; MODEL
College: Faculty of Medicine, Health and Life Sciences
Issue: 43
Start Page: 15173
End Page: 15175