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

链霉菌是丝状细菌，通过顶端延伸和分枝生长形成营养菌丝体。营养枯竭会引发发育程序，导致称为气生菌丝的专门生殖结构的形成，最终导致长链孢子的产生。这一计划在基因和时间上与许多具有重要商业意义的抗生素的生产相协调(链霉菌每年为全球制药业带来400亿美元的收入)。从营养生长到气生菌丝形成的转变受一个调控开关的控制，该开关由sigma因子BldN及其同源的反sigma因子RsbN组成，RsbN是一种跨膜蛋白。BldN表达后，被RsbN保持非活性，RsbN将其隔离在膜上，直到一个未知信号触发RsbN的受控膜内蛋白分解(RIP)并将BldN释放到细胞质中。该项目的目标是确定触发BldN释放的信号并表征使RsbN失活的蛋白分解过程。Bibb，M.J.，Domonkos，Ar.，Chandra，G.和Buttner，M.J.(2012)在Streptomyces venezuelae中的Chaplin和rodlin疏水鞘蛋白的表达受BldN和同源的抗Sigma因子RsbN控制。摩尔。微生物。84：1033-1049.Bush，M.J.，Tschowri，N.，Schlimpert，S.，Flärdh，K.，and Buttner，M.J.(2015)c-di-GMP信号和链霉菌发育转变的调控。自然牧师微生物。13：749-760.Tschowri，N.，Schumacher，M.A.，Schlimpert，S.，Chinnam，N.B.，Findlay，K.C.，Brennan，R.G.，and Buttner，M.J.(2014)四聚体c-di-GMP介导有效的转录因子二聚化以控制链霉菌的发育。158号房：1136-1147。

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.