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Enacyloxins are products of an unusual hybrid modular polyketide synthase encoded by a cryptic burkholderia ambifaria genomic island

Mahenthiralingam, Eshwar, Song, Lijiang, Sass, Andrea, White, Judith, Wilmot, Ceri, Marchbank, Angela Maureen, Boaisha, Othman, Paine, James S., Knight, David William and Challis, Gregory L. 2011. Enacyloxins are products of an unusual hybrid modular polyketide synthase encoded by a cryptic burkholderia ambifaria genomic island. Chemistry & Biology 18 (5) , pp. 665-677. 10.1016/j.chembiol.2011.01.020

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Abstract

Gram-negative Burkholderia cepacia complex (Bcc) isolates were screened for antimicrobial activity against cystic fibrosis microbial pathogens, and the ability of B. ambifaria to inhibit B. multivorans was identified. The activity was mapped to a cluster of cryptic, quorum-sensing-regulated modular polyketide synthase (PKS) genes. Enacyloxin IIa and its stereoisomer designated iso-enacyloxin IIa were identified as metabolic products of the gene cluster, which encoded an unusual hybrid modular PKS consisting of multiple proteins with sequence similarity to cis-acyltransferase (cis-AT) PKSs and a single protein with sequence similarity to trans-AT PKSs. The discovery of the potent activity of enacyloxins against drug-resistant bacteria and the gene cluster that directs their production provides an opportunity for engineered biosynthesis of innovative enacyloxin derivatives and highlights the potential of Bcc bacteria as an underexploited resource for antibiotic discovery.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Chemistry
Biosciences
Cardiff Catalysis Institute (CCI)
Subjects: Q Science > QD Chemistry
Q Science > QH Natural history > QH301 Biology
Publisher: Elsevier
ISSN: 1074-5521
Last Modified: 05 Jan 2018 22:03
URI: http://orca.cf.ac.uk/id/eprint/17346

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Cited 27 times in Web of Science. View in Web of Science.

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