BIOSYNTHESIS OF VITAMIN B12 AND ANAEROBIC METABOLISM

维生素B 12是人体必需的营养素， 只有一些细菌和古菌才能合成需要和能力， 合成B 12在自然界和生理上分布不均匀， B 12在使用它的生物体中的意义尚不确定。(It不是 甚至对人类来说也是如此）。一些动物和所有植物 真菌不需要或使用B12，其他人需要它在他们的饮食。我们 发现所有沙门氏菌的分离株（没有分离株 近缘种E.大肠杆菌）产生B 12（当厌氧生长时）， 将1%的基因组用于合成和运输这种巨大的 辅因子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保持所有的 鲑鱼工作包括实验，以完善我们的理解 合成途径关于B 12用途的工作应提供以下方面的见解： 沙门氏菌厌氧生活方式，并提示B 12 可能在其他生物中发挥作用。B 12合成物的调节行为 基因（cob）表明，B12的主要用途是在厌氧 分解两种碳源，乙醇胺和丙二醇。项目 包括对B 12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 这些分解代谢操纵子编码多种伴随蛋白， 使B12的腺苷酸化，并保护相关酶免受 其他B12类型有迹象表明，每种途径都可能涉及 一个巨大的蛋白质复合体，形成一个细胞器，旨在保护 酶与氧分离或螯合H2O-B12。的机制 coB基因被抑制可能涉及RNA分子识别B 12 因此，可能会提供监管创新， B12在“RNA世界”中的原始起源。B12的演变 途径涉及合成基因的水平转移， 沙门氏菌从另一种细菌。此次收购可能涉及 在沙门氏菌与大肠杆菌的分化中， 致病性生活方式的获得。该项目的相关性， 人类的健康在于既提供洞察力的合成， 人体必需的营养素，并提供背景资料， 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突变体在小鼠中比野生型更具致病性 菌株沙门氏菌的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.)