Biotin catabolism: an unwritten chapter in the metabolism of an essential vitamin

生物素是人类饮食中必不可少的维生素。成人每日所需的足够摄入量 人类的平均摄入量在30-100微克之间。生物素市场分为农业和农业 90%和10%分别用于动物和人类营养。目前 生物素是通过化学合成生产的，其生产水平为>20吨/年。生物素生物合成是 目前，通过发酵生产它的努力正在紧张进行中 对多家生物技术公司进行调查。生物素作为一种辅助因子， 涉及碳酸氢盐作为CO2供体的生化羧化反应。的机理 生物素介导的羧化作用现在已被充分理解。生物素还发现了广泛的 在化学生物学中的应用，其中强烈的生物素抗生物素蛋白相互作用已经被广泛地 用于大分子标记。 与生物素生物合成相反，对生物素催化剂知之甚少。一些产品 以生物素为唯一碳源生长的假单胞菌已被 分离的，但尚未鉴定与生物素催化剂相关的基因或酶。 该建议将集中在生物素分解代谢菌株的分离， 分解代谢操纵子和生物素催化剂中涉及的所有酶的重建。机械论 并将对参与降解的关键酶进行结构研究。 生物素杂环核。

Biotin is an essential vitamin in the human diet. The adequate daily intake for adult humans is in the range of 30-100 micrograms. The biotin market is divided between agricultural and human use with 90% and 10% going to animal and human nutrition respectively. Currently biotin is produced by chemical synthesis at the level of >20 tons/year. Biotin biosynthesis is well-understood and efforts to produce it by fermentation are currently under intense investigation in several biotechnology companies. Biotin functions as a cofactor in all biochemical carboxylation reactions involving bicarbonate as the CO2 donor. The mechanism of biotin mediated carboxylation is now well-understood. Biotin has also found extensive applications in chemical biology where the strong biotin avidin interaction has been extensively used for macromolecular tagging. In contrast to biotin biosynthesis, little is known about biotin catabolism. A few products of biotin catabolism in a soil Pseudomonad grown on biotin as the sole carbon source have been isolated but no genes or enzymes associated with biotin catabolism have yet been identified. This proposal will focus on the isolation of a biotin catabolic strain, the identification of the catabolic operon and the reconstitution of all enzymes involved in biotin catabolism. Mechanistic and structural studies will be carried out on the key enzymes involved in the degradation of the biotin heterocyclic core.