Dissolution of the disparate: Co-ordinate regulation in antibiotic biosynthesis

McLean, Thomas C., Wilkinson, Barrie, Hutchings, Matthew I. and Devine, Rebecca (2019) Dissolution of the disparate: Co-ordinate regulation in antibiotic biosynthesis. Antibiotics, 8 (2). ISSN 2079-6382

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Discovering new antibiotics is vital to combat the growing threat of antimicrobial resistance. Most currently used antibiotics originate from the natural products of actinomycete bacteria, particularly Streptomyces species, that were discovered over 60 years ago. However, genome sequencing has revealed that most antibiotic-producing microorganisms encode many more natural products than previously thought. Biosynthesis of these natural products is tightly regulated by global and cluster situated regulators (CSRs), most of which respond to unknown environmental stimuli, and this likely explains why many biosynthetic gene clusters (BGCs) are not expressed under laboratory conditions. One approach towards novel natural product discovery is to awaken these cryptic BGCs by re-wiring the regulatory control mechanism(s). Most CSRs bind intergenic regions of DNA in their own BGC to control compound biosynthesis, but some CSRs can control the biosynthesis of multiple natural products by binding to several different BGCs. These cross-cluster regulators present an opportunity for natural product discovery, as the expression of multiple BGCs can be affected through the manipulation of a single regulator. This review describes examples of these different mechanisms, including specific examples of cross-cluster regulation, and assesses the impact that this knowledge may have on the discovery of novel natural products.

Item Type: Article
Faculty \ School: Faculty of Science > School of Biological Sciences
Faculty of Science > School of Chemistry
UEA Research Groups: Faculty of Science > Research Groups > Organisms and the Environment
Faculty of Science > Research Groups > Molecular Microbiology
Depositing User: LivePure Connector
Date Deposited: 24 Jun 2019 08:30
Last Modified: 13 May 2023 01:00
URI: https://ueaeprints.uea.ac.uk/id/eprint/71520
DOI: 10.3390/antibiotics8020083


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