There is a real and urgent need for new antimicrobial compounds to combat the rise of multidrug resistant infections. Whole genome sequencing and genome mining have revealed that Streptomyces spp. possess a range of biosynthetic gene clusters for secondary metabolites, however many of them are silent and cryptic under conventional laboratory conditions. It has also been shown that triggering the expression of these cryptic gene clusters in Streptomyces might yield novel antibiotics. Here, we isolated over 100 Streptomyces strains from sediments contaminated with heavy metals from a former industrial site in Scotland, United Kingdom. These strains were assayed for heavy metal dependent antimicrobial activity. We have used a combination of genomics, bioinformatics and transcriptomics to investigate these novel strains, providing a phylogenetic context and molecular evidence towards the discovery of the gene clusters responsible for antibiotic biosynthesis.Our findings highlight the potential of using heavy metals for activation of silent biosynthetic metabolite gene clusters in Streptomyces isolated from extreme environments for natural product discovery. These findings are supported by the fact that these compounds are produced only in the presence of sub-inhibitory concentrations of heavy metals but not in the absence of metal induction. Whole genome sequencing has enabled us to investigate the taxonomy and biosynthetic capacity of the strains whilst transcriptomic analysis and bioinformatics tools are allowing us to investigate the changes in the transcript levels of these genes that occur under metal-inducing conditions.
|Date of Award||15 Dec 2017|
- University Of Strathclyde
|Supervisor||Nicholas Tucker (Supervisor) & Paul Hoskisson (Supervisor)|