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

生物素分解代谢：必需维生素代谢中不成文的章节

• 批准号: 10346796
• 负责人: TADHG P. BEGLEY
• 金额: $ 36.7万
• 依托单位: TEXAS A&M UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-12-05 至 2025-11-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10346796
• 关键词: Acids; Adult; Agriculture; Anabolism; Animals; Avidin; Bicarbonates; Biochemical; Biology; Biotechnology; Biotin; Carbon; Carbon Dioxide; Carbonic Acid; Catabolism; Chemicals; Chemistry; Cloning; Diet; Enzymatic Biochemistry; Enzymes; Evaluation; Excision; Fatty Acids; Fermentation; Genes; Genome; Human; Intake; Investigation; Kinetics; Knowledge; Logic; Mediating; Metabolism; Operon; Pathway interactions; Principal Investigator; Reaction; Role; Route; Sequence Analysis; Side; Soil; Source; Testing; Vitamins; analog; base; carboxylation; chemical synthesis; cofactor; enzyme reconstitution; gut microbiome; novel; nutrition; overexpression; oxidation; programs; reconstitution; tetrahydrothiophene; vitamin metabolism

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.

生物素是人类饮食中必不可少的维生素。成人的每日摄入量足够 人类在30-100微克的范围内。生物素市场在农业之间分配 人类使用分别用于动物和人类营养的90％和10％的使用。现在 生物素是通过化学合成在> 20吨/年的水平上产生的。生物素生物合成是 众所周知和通过发酵生产它的努力目前正在强烈 在几家生物技术公司进行调查。生物素在所有人中充当辅助因子 涉及碳酸氢盐作为CO2供体的生化羧化反应。机制 生物素介导的羧化现在已被众所周知。生物素也发现了广泛的 在化学生物学中的应用，其中强生物素抗原素相互作用已广泛 用于大分子标记。 与生物素生物合成相反，对生物素分解代谢知之甚少。几种产品 在生物素上生长的土壤假单胞菌中的生物素分解代谢，因为唯一的碳源已经是 尚未鉴定出与生物素分解代谢相关的基因或酶。 该建议将集中于生物素分解代谢菌株的隔离，鉴定 分解代谢操纵子和所有参与生物素分解代谢的酶的重构。机理 并将对与降解的关键酶进行结构研究 生物素杂环核。