Multiplicity and functional diversity of cyclic mononucleotide signaling in Sinorhizobium meliloti

苜蓿中华根瘤菌环状单核苷酸信号的多样性和功能多样性

• 批准号: 314772579
• 负责人: Professorin Dr. Anke Becker
• 金额: --
• 依托单位: Zentrum für Synthetische Mikrobiologie (SYNMIKRO)
• 依托单位国家: 德国
• 项目类别: Priority Programmes
• 财政年份: 2016
• 资助国家: 德国
• 起止时间: 2015-12-31 至 2023-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/314772579?language=en
• 关键词: Multiplicity; functional; diversity; cyclic; mononucleotide

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.

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模块并行操作的新概念，该概念在过去十年中得到了详细研究。相比之下，微生物学中对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的研究很少。我们对α-变形菌根瘤菌科共生固氮成员基因组的计算分析揭示了这些细菌中异常大量的腺苷酸/鸟苷酸环化酶（AC/GC）基因。苜蓿中华根瘤菌菌株 Rm2011 含有 28 个 III 类 AC/GC 基因、10 个编码 CRP 样蛋白的基因和 7 个编码可水解环状单核苷酸的磷酸二酯酶 (PDE) 的基因。根据催化 CHD 和其他非催化结构域的组织，编码的 AC/GC 蛋白可分为九个亚类。初步工作已经证明了苜蓿中华根瘤菌的 cAMP 和 cGMP 合成和分泌，并提供了大多数这些 AC/GC 和 CRP 样蛋白的活性的初步表征。与 cAMP/cGMP 信号传导相关的成分的多样性以及基因操作的良好可及性使苜蓿中华根瘤菌成为理想的模型系统。我们的首要目标是了解苜蓿中华草中环状单核苷酸信号传导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该模型生物中 cAMP/cGMP 信号传导的调节输出。最终，我们的见解将允许在优先计划 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。