Abstract
Microbes are a major source of antibiotics, pharmaceuticals, and other bioactive compounds. The production of many specialized microbial metabolites is encoded in biosynthetic gene clusters (BGCs). A challenge associated with natural product discovery is that many BGCs are not expressed under laboratory growth conditions. Here we report a genome-mining approach to discover BGCs with luxR-type quorum sensing (QS) genes, which code for regulatory proteins that control gene expression. Our results show that BGCs linked to genes coding for LuxR-like proteins are widespread in Proteobacteria. In addition, we show that associations between luxR homolog genes and BGCs have evolved independently many times, with functionally diverse gene clusters. Overall, these clusters may provide a source of new natural products for which there is some understanding about how to elicit production. IMPORTANCE Bacteria biosynthesize specialized metabolites with a variety of ecological functions, including defense against other microbes. Genes that code for specialized metabolite biosynthetic enzymes are frequently clustered together. These BGCs are often regulated by a transcription factor encoded within the cluster itself. These pathway-specific regulators respond to a signal or indirectly through other means of environmental sensing. Many specialized metabolites are not produced under laboratory growth conditions, and one reason for this issue is that laboratory growth media lack environmental cues necessary for BGC expression. Here, we report a bioinformatics study that reveals that BGCs are frequently linked to genes coding for LuxR family QS-responsive transcription factors in the phylum Proteobacteria. The products of these luxR homolog-associated gene clusters may serve as a practical source of bioactive metabolites.
Highlights
Microbes are a major source of antibiotics, pharmaceuticals, and other bioactive compounds
We found that luxR-type quorum sensing (QS)-associated biosynthetic gene clusters (BGCs) make up about 2.9% of BGCs encoded by bacteria in the phylum Proteobacteria; the antiSMASH database contains 72,178 BGCs encoded by Proteobacteria, and our unfiltered list of luxR homolog-associated BGCs contained 2,081 hits
Our results suggest that luxR homolog-associated BGCs are common and widely distributed within bacteria belonging to the phylum Proteobacteria
Summary
Microbes are a major source of antibiotics, pharmaceuticals, and other bioactive compounds. Genes that code for specialized metabolite biosynthetic enzymes are frequently clustered together These BGCs are often regulated by a transcription factor encoded within the cluster itself. We report a bioinformatics study that reveals that BGCs are frequently linked to genes coding for LuxR family QS-responsive transcription factors in the phylum Proteobacteria. The products of these luxR homolog-associated gene clusters may serve as a practical source of bioactive metabolites. Researchers have found various means to activate the expression of silent clusters, an understanding of the regulatory circuits that control BGCs of interest would provide a major practical advantage to the discovery and study of the encoded product(s) [5]. QS-based gene regulation has been studied in many organisms, including Gram-negative and Grampositive bacteria, and involves a variety of signal molecules [6, 7]
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