The regulation of development in the antibiotic-producing bacteria Streptomyces (BUTTNER_J17DTP)

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Streptomycetes are filamentous bacteria that grow by tip extension and branching to form a vegetative mycelium. Nutrient depletion triggers a developmental program that leads to the formation of specialized reproductive structures called aerial hyphae, which ultimately give rise to long chains of spores. This program is genetically and temporally coordinated with the production of numerous commercially important antibiotics (Streptomycetes account for $40 billion of revenue annually in the pharmaceutical industry worldwide). The transition from vegetative growth to the formation of aerial hyphae is controlled by a regulatory switch consisting of a sigma factor, BldN, and its cognate anti-sigma, RsbN, a transmembrane protein. After BldN is expressed, it is held inactive by RsbN, which sequesters it to the membrane, until an unknown signal triggers Regulated Intramembrane Proteolysis (RIP) of RsbN and release of BldN into the cytoplasm. The goals of this project are to identify the signal that triggers release of BldN and to characterize the proteolytic process that inactivates RsbN.Bibb, M.J., Domonkos, Á., Chandra, G., and Buttner, M.J. (2012) Expression of the chaplin and rodlin hydrophobic sheath proteins in Streptomyces venezuelae is controlled by BldN and a cognate anti-sigma factor, RsbN. Mol. Microbiol. 84:1033-1049.Bush, M.J., Tschowri, N., Schlimpert, S., Flärdh, K., and Buttner, M.J. (2015) c-di-GMP signalling and the regulation of developmental transitions in streptomycetes. Nature Rev. Microbiol. 13:749-760.Tschowri, N., Schumacher, M.A., Schlimpert, S., Chinnam, N.B., Findlay, K.C., Brennan, R.G., and Buttner, M.J. (2014) Tetrameric c-di-GMP mediates effective transcription factor dimerization to control Streptomyces development. Cell 158:1136-1147.