Studies of a bacterial B12 adenosyltransferase homologous to the human enzyme

描述（由申请人提供）：从基础科学的角度来看，对辅酶B12生物合成等主要代谢途径的详细分析提供了一个极好的机会来研究辅酶功能的复杂性，以及蛋白质之间导致酶复合物形成和功能的迷人相互作用。将结构生物学家、化学家和生理学家聚集在一起的多面方法可能会产生单一学科方法无法提供的理解水平。我们有机会继续模拟一个主要的生物合成途径，它广泛分布于所有形式的生命中，除了植物。我们也有机会继续学习不同环境下的细胞所使用的策略，将环境中前体的同化与这种重要辅酶的新生生物合成结合起来。从教育的角度来看，辅酶B12生物合成的研究为年轻的研究人员提供了一个在细胞生理学方面进行广泛训练的机会，为后基因组学时代的研究提供了重要的人力资源。从社会的角度来看，钴胺素的研究延伸到许多其他领域，如哺乳动物的抗肿瘤作用，过度镇静的治疗，以及在衰老过程中的可能作用。人体内钴胺素代谢紊乱可导致丙酸、甲基丙二酸和生物素代谢紊乱。脂溶性钴胺素类似物已被报道为跨膜的选择性离子载体。在诸如原核生物这样的简单生物体中，B12参与tRNA的成熟，并已被用于生物修复工作，以清除环境中的人为污染物。B12和类B12化合物的潜在工业用途包括合成有机化学的催化剂。更好地了解罗伊氏乳杆菌中的B12腺苷化是可取的，因为这种细菌被用作乳制品中的益生菌，以改善人类的营养和健康。

DESCRIPTION (provided by applicant): From the basic science perspective, the detailed analysis of a major metabolic pathway such as the one dedicated to coenzyme B12 biosynthesis offers an excellent opportunity to investigate the complexities of coenzyme function, and the fascinating interactions amongst proteins leading to enzyme complex formation and function. A multifaceted approach that brings together structural biologists, chemists, and physiologists is likely to result in a level of understanding not afforded by single-discipline approaches. We have the opportunity to continue modeling a major biosynthetic pathway that is widely distributed amongst all forms of life, with the exception of plants. We also have an opportunity to continue learning about strategies used by cells that occupy vastly different environments to integrate the assimilation of precursors from the environment with de novo biosynthesis of this important coenzyme. From an educational standpoint, research on coenzyme B12 biosynthesis offers an opportunity for young investigators to train broadly in cell physiology, providing a critical human resource for research in the post- genomics era. From a societal standpoint, cobalamin research extends into many other areas such as antitumor effects in mammals, treatment for oversedation, and possible roles in the process of ageing. Malfunction of cobalamin metabolism in humans leads to disorders of propionate, methylmalonate and biotin metabolism. Liposoluble cobalamin analogs have been reported as selective ion carriers across membranes. In 'simpler1 organisms such as prokaryotes, B12 is involved in tRNA maturation, and has been used in bioremediation efforts to remove man made pollutants from the environment. Potential industrial uses for of B12 and B12-like compounds include catalysts in synthetic organic chemistry. A better understanding of B12 adenosylation in Lactobacillus reuteri is desirable because this bacterium is used as a probiotic in dairy products to improve human nutrition and health.