Specialized and shared functions of diguanylate cyclases and phosphodiesterases inStreptomycesdevelopment
Specialized and shared functions of diguanylate cyclases and phosphodiesterases inStreptomycesdevelopment
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DOI：
10.1111/mmi.14581
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发表时间：
2020-08-14
影响因子：
3.6
通讯作者：
Tschowri, Natalia
中科院分区：
文献类型：
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作者：
Haist, Julian;Neumann, Sara Alina;Tschowri, Natalia
第二信使二-3,5-环二鸟苷单磷酸（c-di-GMP）决定链霉菌何时开始产孢。c-di-GMP信号通过调节因子BldD和sigma因子sigma（whg）整合到遗传分化网络中。然而，发育特异性二胍酸环化酶（DGCs） CdgB和CdgC以及c-二gmp磷酸二酯酶（PDEs） RmdA和RmdB的功能尚不清楚。在这里，我们提供了GGDEF-EAL结构域蛋白RmdB来自的生化证据。委内瑞拉是一种单功能PDE，可将c-二- gmp水解为5 ' pGpG。尽管具有等效的GGDEF-EAL结构域排列，RmdA将c-di-GMP切割为GMP，并显示剩余的DGC活性。我们发现，完整的EAL基序对于这两种酶的体内功能至关重要，因为表达带有AAA基序而不是EAL的蛋白变体的菌株在发育中延迟，类似于无突变体。对增量cdgB、增量cdgC、增量rmdA和增量rmdb菌株的转录组分析表明，这些酶指定的c-di-GMP具有全局调控作用，约占all的20%。委内瑞拉基因在dgc突变体中差异表达。我们的数据表明，决定产孢时间和模式的主要c-di- gmp控制目标是参与细胞分裂和覆盖链霉菌菌丝和孢子的疏水鞘产生的基因。
The second messenger bis-3,5-cyclic di-guanosine monophosphate (c-di-GMP) determines whenStreptomycesinitiate sporulation. c-di-GMP signals are integrated into the genetic differentiation network by the regulator BldD and the sigma factor sigma(WhiG). However, functions of the development-specific diguanylate cyclases (DGCs) CdgB and CdgC, and the c-di-GMP phosphodiesterases (PDEs) RmdA and RmdB, are poorly understood. Here, we provide biochemical evidence that the GGDEF-EAL domain protein RmdB fromS. venezuelaeis a monofunctional PDE that hydrolyzes c-di-GMP to 5 ' pGpG. Despite having an equivalent GGDEF-EAL domain arrangement, RmdA cleaves c-di-GMP to GMP and exhibits residual DGC activity. We show that an intact EAL motif is crucial for the in vivo function of both enzymes since strains expressing protein variants with an AAA motif instead of EAL are delayed in development, similar to null mutants. Transcriptome analysis of increment cdgB, increment cdgC, increment rmdA,and increment rmdBstrains revealed that the c-di-GMP specified by these enzymes has a global regulatory role, with about 20% of allS. venezuelaegenes being differentially expressed in thecdgCmutant. Our data suggest that the major c-di-GMP-controlled targets determining the timing and mode of sporulation are genes involved cell division and the production of the hydrophobic sheath that coversStreptomycesaerial hyphae and spores.