BIOSYNTHESIS OF VITAMIN B12 AND ANAEROBIC METABOLISM

维生素B12是人类的一种基本营养素，可能是 仅由一些细菌和古菌合成的。需要和能力来 合成B12在自然界中分布不均，生理上 B12在使用它的生物体中的意义尚不确定。(不是 即使对人类来说也是完全清楚的。)一些动物，显然是所有的植物 真菌不需要或不使用B12，其他人在他们的饮食中需要B12。我们 发现所有沙门氏菌分离株(没有分离到其 近亲，大肠杆菌)产生B12(厌氧生长时)和 将它们1%的基因组用于合成和运输这种巨大的 辅因。该项目旨在更好地了解 这种维生素以及为什么它的合成一直由所有 沙门氏菌。工作包括实验，以完善我们对 合成途径。关于B12用途的研究应该提供对 沙门氏菌的厌氧生活方式，应该建议B12 可能在其他生物体中发挥作用。B12合成物的调节行为 基因(Cob)表明B12的主要用途是在厌氧 乙醇胺和丙二醇这两种碳源的细目。该项目 包括对B12和两个操纵子的合成基因的研究 乙醇胺(EUT)和丙二醇(PDU)的利用途径。两者都有 在这些分解代谢操纵子中，编码多种伴随蛋白出现 使B12的腺苷酸化并保护相关酶不受抑制 其他B12表格。有迹象表明，每条途径都可能涉及一种 巨大的蛋白质复合体，形成一个细胞器，旨在保护 酶从氧气或以隔离ADO-BL2。这是一种机制 COB基因被抑制可能与RNA分子对B12的识别有关 因此可以提供监管的新颖性，让人回想起 BL2在“RNA世界”中的原始起源。BL2的演变 途径涉及合成基因的水平转移到 沙门氏菌来自另一种细菌。这笔收购可能涉及 在沙门氏菌与大肠杆菌的分化中，并与 养成致病的生活方式。该项目与以下方面的相关性 人类的健康既在于提供对一种 和提供背景信息，这些背景信息可能 对了解沙门氏菌与动物宿主的相互作用很重要。 (沙门氏菌cob突变株对小鼠的致病性比野生型更强 菌株。沙门氏菌eut突变损害了在 宿主巨噬细胞。)

Vitamin B 12 is an essential nutrient for humans that is probably synthesized only by some bacteria and archaea. The need and ability to synthesize B 12 is unevenly distributed in nature and the physiological significance of B 12 in the organisms that use it is uncertain. (It's not completely clear even for humans.) Some animals and apparently all plants and fungi do not need or use B12, others require it in their diet. We discovered that the all isolates of Salmonella (and no isolates of their near relative, E. coli) make B 12 (when growing anaerobically) and dedicate 1% of their genome to the synthesis and transport of this huge cofactor. This project is aimed at better understanding the synthesis of this vitamin and why its synthesis has been maintained by all the Salmonellae. Work includes experiments to refine our understanding of the synthetic pathway. Work on the uses of B 12 should provide insights into the anaerobic lifestyle of Salmonella and should suggest roles that B 12 may play in other organisms. The regulatory behavior of the B 12 synthetic genes (cob) suggests that the main use of B12 is in the anaerobic breakdown of two carbon sources, ethanolamine and propanediol. The project includes work on the synthetic genes for B 12 and two operons that encode the utilization pathways of ethanolamine (eut) and propanediol (pdu). Both of these catabolic operons encode multiple attendant proteins that appear to adenosylate of B12 and protect the relevant enzyme from inhibition by other B12 forms. There are indications that each pathway may involve a huge complex of proteins that forms an organelle designed to protect the enzymes from oxygen or to sequester Ado-Bl2. The mechanism by which the cob genes are repressed may involve recognition of B 12 by an RNA molecule and therefore may provide regulatory novelties that hearken back to the primitive origins of Bl2 in the "RNA world". The evolution of the Bl2 pathway has involved horizontal transfer of the synthetic genes into Salmonella from another bacterium. This acquisition may have been involved in the divergence of Salmonella from E coli and is correlated with acquisition of pathogenic lifestyle. The relevance of this project to human health lies both in providing insights into the synthesis of an essential human nutrient and in providing background information that may be important to understanding Salmonella's interaction with animal hosts. (Salmonella cob mutants are more pathogenic in mice than wild type strains. Salmonella eut mutations are impaired for ability to survive in a host macrophage.)