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

链霉菌是丝状细菌，其通过尖端延伸和分支生长以形成营养菌丝体。营养物质的耗尽会触发一个发育程序，导致形成称为气生菌丝的专门生殖结构，最终产生长链的孢子。该计划在基因和时间上与许多商业上重要的抗生素的生产相协调（链霉菌每年在全球制药业中占400亿美元的收入）。从营养生长到气生菌丝形成的转变由一个调节开关控制，该调节开关由σ因子BldN及其同源反σ因子RsbN（一种跨膜蛋白）组成。在BldN表达后，它被RsbN保持无活性，RsbN将其隔离到膜上，直到未知信号触发RsbN的调节性膜内蛋白水解（RIP）并将BldN释放到细胞质中。该项目的目标是鉴定触发BldN释放的信号并表征使RsbN失活的蛋白水解过程。Domonkos，科罗拉多州，Chandra，G.，和Buttner，M. J.（2012）委内瑞拉链霉菌中卓别林和rodlin疏水鞘蛋白的表达受BldN和同源抗σ因子RsbN控制。摩尔Microbiol. 84：1033- 1049. Bush，M.J.，Tschowri，N.，Schlimpert，S.，Flärdh，K.，Buttner，M. J.（2015）c-di-GMP信号传导和链霉菌发育转变的调节。自然评论微生物学。13：749- 760. Tschowri，N.，舒马赫，文学硕士，Schlimpert，S.，Chinnam，N.B.，芬德利，K.C.，布伦南，RG，和Buttner，M.J.（2014）Tetrameric c-di-GMP mediates effective transcription factor dimerization to control Streptomyces development.细胞158：1136-1147.

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.