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Biosynthesis of a new skyllamycin in <i>Streptomyces nodosus</i>: a cytochrome P450 forms an epoxide in the cinnamoyl chain

Yuhao Song Orcid Logo, Jose A. Amaya, Vidhi C. Murarka Orcid Logo, Hugo Mendez, Mark Hogan Orcid Logo, Jimmy Muldoon Orcid Logo, Paul Evans Orcid Logo, Yannick Ortin Orcid Logo, Steven Kelly Orcid Logo, David Lamb Orcid Logo, Thomas L. Poulos, Patrick Caffrey Orcid Logo

Organic and Biomolecular Chemistry, Volume: 22, Issue: 14, Pages: 2835 - 2843

Swansea University Authors: Steven Kelly Orcid Logo, David Lamb Orcid Logo

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DOI (Published version): 10.1039/d4ob00178h

Abstract

Activation of a silent gene cluster in Streptomyces nodosus leads to synthesis of a cinnamoyl-containing non-ribosomal peptide (CCNP) that is related to skyllamycins. This novel CCNP was isolated and its structure was interrogated using mass spectrometry and nuclear magnetic resonance spectroscopy....

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Published in: Organic and Biomolecular Chemistry
ISSN: 1477-0520 1477-0539
Published: Royal Society of Chemistry (RSC) 2024
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URI: https://cronfa.swan.ac.uk/Record/cronfa66030
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Abstract: Activation of a silent gene cluster in Streptomyces nodosus leads to synthesis of a cinnamoyl-containing non-ribosomal peptide (CCNP) that is related to skyllamycins. This novel CCNP was isolated and its structure was interrogated using mass spectrometry and nuclear magnetic resonance spectroscopy. The isolated compound is an oxidised skyllamycin A in which an additional oxygen atom is incorporated in the cinnamoyl side-chain in the form of an epoxide. The gene for the epoxide-forming cytochrome P450 was identified by targeted disruption. The enzyme was overproduced in Escherichia coli and a 1.43 Å high-resolution crystal structure was determined. This is the first crystal structure for a P450 that forms an epoxide in a substituted cinnamoyl chain of a lipopeptide. These results confirm the proposed functions of P450s encoded by biosynthetic gene clusters for other epoxidized CCNPs and will assist investigation of how epoxide stereochemistry is determined in these natural products.
Keywords: cytochrome P450; Streptomyces; skyllamycin; antibiotic; epoxidation
College: Faculty of Medicine, Health and Life Sciences
Issue: 14
Start Page: 2835
End Page: 2843