Genome mining and manipulation of Streptomyces genomes to identify new natural products

Orateur : Pierre LEBLOND (Université de Lorraine, UMR INRA 1128 Dynamique des Génomes et Adaptation Microbienne, Dynamic)

Natural products from microorganisms and plants are compounds of utmost importance because of their bro ad spectrum of applications in human and veterinary therapy and in agriculture. Search for new bioactive natural products remains essential. For example, emerging resistant pathogenic bacteria, a public health major concern, highlights the pressing need for new antibiotics. Most of the commercial antibiotics are produced by the bacterial genus Streptomyces and analysis of genome sequences has revealed the presence of numerous cryptic secondary metabolite gene clusters disclosing t he hitherto untapped wealth of Streptomyces in producing bioactive molecules. Our model, the industrial strain Streptomyces ambofaciens, was known since decades to produce only two antibiotics, the macrolide spiramycin, an antibacterial agent also used for treating Toxoplasma infections, and the pyrrole-amide congocidine. Bioinformatics analyses of its genome sequence have identified 21 gene clusters encoding cryptic natural product biosynthetic pathways, not associated with the production of known metabolites. Different approaches have been developed to taking full advantage of the metabolic capabilities of S. ambofaciens. Up to now, they allowed us to identify two new antimicrobial compounds and volatiles never described as being produced by S. ambofaciens and to discover of a new family of 51-membered macrolides with promising anti-cancer activity.

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