Multiplicity and functional diversity of cyclic mononucleotide signaling in Sinorhizobium meliloti

合成和降解普遍存在的细菌第二信使c-di-GMP的酶的多样性和多样性的发现，提出了高度特异性的基于第二信使的信号传导模块并行操作的新概念，这在过去十年中得到了非常详细的研究。相比之下，合成环状单核苷酸第二信使cAMP和/或cGMP的环化酶的多样性和功能多样化在微生物学中很少被研究。我们对α -变形细菌根瘤菌科共生固氮成员的基因组进行计算分析，发现这些细菌中腺苷酸/鸟苷酸环化酶（AC/GC）基因的数量异常高。meliloti Sinorhizobium meliloti菌株Rm2011含有28个III类AC/GC基因，10个编码crp样蛋白的基因和7个编码磷酸二酯酶（PDEs）的基因，这些基因可以水解环单核苷酸。根据催化CHD和其他非催化结构域的组织，编码的AC/GC蛋白可分为9个亚类。初步研究表明，S. meliloti可以合成和分泌cAMP和cGMP，并初步表征了这些AC/GC和crp样蛋白的活性。cAMP/cGMP信号相关成分的多样性和良好的遗传操作可及性使其成为理想的模型系统。我们的首要目标是了解环单核苷酸信号在S. meliloti中的多样性和功能多样化的作用。我们提出了一项研究计划，将探索单核苷酸环化酶和pde的催化活性和生物学作用，单核苷酸环化酶的感觉输入，以及cAMP/cGMP信号的调节输出。最终，我们的见解将允许在优先项目SPP 1879的框架内比较细菌c-di-GMP和cAMP/cGMP信号网络功能多样化的分子原理。

Discovery of the multiplicity and diversity of enzymes synthesizing and degrading the ubiquitous bacterial second messenger c-di-GMP has raised the new concept of parallel operation of highly specific second messenger-based signaling modules, which has been studied in great detail during the last decade. In contrast, multiplicity and functional diversification of cyclases synthesizing the cyclic mononucleotide second messengers cAMP and/or cGMP is poorly investigated in microbiology. Our computational analysis of genomes of symbiotic nitrogen fixing members of the alpha-proteobacterial Rhizobiaceae revealed an exceptionally high number of adenylate/guanylate cyclase (AC/GC) genes in these bacteria. Sinorhizobium meliloti strain Rm2011 harbors 28 class III AC/GC genes, ten genes encoding CRP-like proteins and seven genes encoding phosphodiesterases (PDEs) that may hydrolyze cyclic mononucleotides. According to the organization of catalytic CHD and additional non-catalytic domains the encoded AC/GC proteins can be grouped into nine subclasses. Preliminary work has demonstrated cAMP and cGMP synthesis and secretion by S. meliloti and provided an initial characterization of the activities of most of these AC/GC and CRP-like proteins. The high variety in components related to cAMP/cGMP signaling and the excellent accessibility to genetic manipulations make S. meliloti an ideal model system. Our overarching goal is to understand the role of multiplicity and functional diversification of cyclic mononucleotide signaling in S. meliloti. We propose a research plan that will explore the catalytic activities and biological roles of mononucleotide cyclases and PDEs, the sensory input to mononucleotide cyclases, and the regulatory output of cAMP/cGMP signaling in this model organism. Ultimately, our insights will allow for comparisons of the molecular principles underlying functional diversification in bacterial c-di-GMP and cAMP/cGMP signaling networks in the framework of the priority program SPP 1879.