Exploring new avenues of growth and secondary metabolite production by antibiotic-producing Streptomyces bacteria

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Streptomyces bacteria are of major scientific interest due to their extraordinary life cycle and their prolific secondary metabolism, the products of which include the majority of clinically prescribed antibiotics. The metabolic potential of the streptomycetes has not been fully exploited, and they are looked upon as being important sources of new antibiotics that can help in treating antibiotic resistant infections. A more holistic understanding of Streptomyces biology will allow for effective exploitation of their unique metabolic and developmental capabilities. Recent work has revealed the model organism Streptomyces venezuelae can abscond from its classical life cycle when confronted with fungi or a nutrient-poor environment, using a newly described growth behaviour called exploratory growth. Explorer cells grow as non-branching vegetative hyphae and have a much faster growth rate compared with the "normal" vegetative hyphae. Interestingly, exploration does not dependent on classical developmental regulators, suggesting it represents a new form of growth. Streptomyces exploration provides an outstanding system with which to elucidate the molecular and regulatory mechanisms of microbial communication, microbial development and secondary metabolism. Based on RNA-sequencing analyses and chemical mutagenesis, several genes have been confirmed to be involved in the regulation of exploratory growth. Additionally, altered expression of secondary metabolite clusters has been detected. Using complementary genetic, biochemical, cell biological and metabolic analyses, the proposed project will investigate how exploration is regulated, with special focus on the unique mechanism of colony expansion, and how exploration affects secondary metabolite production. This project is expected to provide novel insights into central molecular mechanisms within microbial communities. Furthermore, the identification of novel natural products is likely to be an intrinsic part of the proposed research.