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Enacyloxins are products of an unusual hybrid modular polyketide synthase encoded by a cryptic burkholderia ambifaria genomic island
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Mahenthiralingam, Eshwar, Song, Lijiang, Sass, Andrea, White, J. (Judith), Wilmot, Ceri, Marchbank, Angela, Boaisha, Othman, Paine, James, Knight, D. (David) 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, Vol.18 (No.5). pp. 665-677. ISSN 1074-5521
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Official URL: http://dx.doi.org/10.1016/j.chembiol.2011.01.020
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-acyl-transferase (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: | Journal Article |
|---|---|
| Subjects: | Q Science > QD Chemistry Q Science > QR Microbiology R Medicine > RM Therapeutics. Pharmacology |
| Divisions: | Faculty of Science > Chemistry |
| Library of Congress Subject Headings (LCSH): | Gram-negative bacteria, Cystic fibrosis -- Treatment, Biosynthesis, Antibiotics |
| Journal or Publication Title: | Chemistry & Biology |
| Publisher: | Cell Press |
| ISSN: | 1074-5521 |
| Date: | 27 May 2011 |
| Volume: | Vol.18 |
| Number: | No.5 |
| Page Range: | pp. 665-677 |
| Identification Number: | 10.1016/j.chembiol.2011.01.020 |
| Status: | Peer Reviewed |
| Publication Status: | Published |
| Access rights to Published version: | Restricted or Subscription Access |
| Funder: | Cystic Fibrosis Foundation, European Regional Development Fund (EDRF), Advantage West Midlands (AWM) |
| Grant number: | MAHENT06V0 (CFF) |
| URI: | http://wrap.warwick.ac.uk/id/eprint/40052 |
Data sourced from Thomson Reuters' Web of Knowledge
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