BIOSYNTHESIS OF VITAMIN B12 AND ANAEROBIC METABOLISM

维生素 B12 的生物合成和无氧代谢

基本信息

批准号：
2444597
负责人：
JOHN R ROTH
金额：
$ 30.03万
依托单位：
UNIVERSITY OF UTAH
依托单位国家：
美国
项目类别：
财政年份：
1985
资助国家：
美国
起止时间：
1985-07-01 至 1999-06-30
项目状态：
已结题

项目摘要

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.)

维生素B 12是人类必不可少的营养素仅由一些细菌和古细菌合成。需要和能力综合B 12在自然界和生理上分布不均匀 B 12在使用它的生物中的意义是不确定的。（它不是即使人类也完全清楚。）一些动物，显然所有植物真菌不需要或不需要B12，其他人则需要饮食。我们发现沙门氏菌的所有分离株都没有接近亲戚，大肠杆菌）使B 12（厌氧生长时）和将其1％的基因组献给了这个巨大的综合和运输辅因子。该项目旨在更好地理解合成这种维生素以及为什么所有的合成沙门氏菌。工作包括实验以完善我们对合成途径。在B 12的使用方面的工作应提供见解沙门氏菌的厌氧生活方式，应该表明b 12 可能会在其他生物体中发挥作用。 B 12合成的调节行为基因（COB）表明B12的主要用途是在厌氧中两个碳源分解，乙醇胺和丙二醇。项目包括B 12的合成基因和两个编码的操纵子的工作乙醇胺（EUT）和丙二醇（PDU）的利用途径。两个都这些分解代谢操纵子编码出现的多种伴随蛋白以B12的腺苷酸化并保护相关酶免受抑制作用其他B12表格。有迹象表明每条途径可能涉及大量的蛋白质复合物，形成一个旨在保护该细胞器的细胞器来自氧气或隔离ado-bl2的酶。该机制抑制棒基因可能涉及RNA分子对B 12的识别因此，可能会提供监管新颖性，使 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来自另一种细菌的沙门氏菌。此收购可能涉及在沙门氏菌与E大肠杆菌的分歧中，与获得致病生活方式。这个项目与人类健康在于提供有关合成的见解基本的人类营养素，并提供可能的背景信息了解沙门氏菌与动物宿主的互动很重要。（沙门氏菌棒突变体在小鼠中比野生型更致病菌株。沙门氏菌EUT突变因能够生存的能力而受到损害宿主巨噬细胞。）