Studies of a bacterial B12 adenosyltransferase homologous to the human enzyme

描述(申请人提供)：从基础科学的角度，对主要代谢途径的详细分析，如辅酶B12的生物合成，提供了一个极好的机会来研究辅酶功能的复杂性，以及导致酶复合体形成和功能的蛋白质之间有趣的相互作用。将结构生物学家、化学家和生理学家聚集在一起的多方面方法可能会导致单一学科方法无法提供的理解水平。我们有机会继续模拟广泛分布在所有生命形式中的主要生物合成途径，植物除外。我们还有机会继续学习细胞所使用的策略，这些细胞占据着非常不同的环境，将来自环境的前体的同化与这种重要辅酶的从头生物合成结合在一起。从教育的角度来看，辅酶B12生物合成的研究为年轻研究人员提供了一个广泛培训细胞生理学的机会，为后基因组时代的研究提供了关键的人力资源。从社会的角度来看，钴胺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，以及在衰老过程中可能扮演的角色。人体钴胺代谢障碍导致丙酸、丙二酸甲酯和生物素代谢紊乱。脂溶性钴胺类似物已被报道为跨膜选择性离子载体。在更简单的生物中，如原核生物，B12参与tRNA的成熟，并已被用于从环境中去除人为污染物的生物修复努力。B12和类似B12的化合物的潜在工业用途包括合成有机化学中的催化剂。更好地了解鲁氏乳杆菌中的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.