Studies of a bacterial B12 adenosyltransferase homologous to the human enzyme

点击翻译按钮获取中文摘要

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.