PORPHYRIN AND CORRINOID BIOSYNTHESIS

卟啉和类咕啉生物合成

• 批准号: 7187425
• 负责人: Frank M. Raushel
• 金额: $ 51.76万
• 依托单位: TEXAS A&M UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1982
• 资助国家: 美国
• 起止时间: 1982-06-01 至 2009-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7187425
• 关键词: Accounting; Acetates; Acute Intermittent Porphyria; Address; Aerobic; Aerobic Bacteria; Anabolism; Anaerobic Bacteria; Anemia; Archaea; Biological Factors; Chemistry; Chlorophyll; Chromosome Mapping; Cobalt; Complex; Corrinoids; Disease; Engineering; Enzymatic Biochemistry; Enzymes; Event; Genes; Goals; Grant; Heme; Hydroxyl Radical; Hydroxymethylbilane Synthase; In Vitro; Isomerase; Knowledge; Label; Life; Mediating; Methanobacteria; Methanobacterium; Methylation; Molecular Biology; NMR Spectroscopy; Organic Chemistry; Organism; Pathway interactions; Pigments; Porphobilinogen Synthase; Porphyrins; Positioning Attribute; Propionates; Propionibacterium; Protein Overexpression; Pseudomonas; Route; Running; Salmonella typhimurium; Uroporphyrinogen III; Uroporphyrinogens; Vitamin B 12; Vitamins; X ray diffraction analysis; X-Ray Diffraction; analog; base; cobyrinic acid; corrin; enzyme mechanism; enzyme pathway; inhibitor/antagonist; insight; methyl group; precorrin 3; reconstitution

Using a combination of organic chemistry, molecular biology, enzymology, and NMR spectroscopy the details of the biosynthesis of uroporphyrinogen III (theprecursor of heme and chlorophyll) and its subsequent transformation to vitamin B12,the anti-perinicious anemia factor, will be elucidated. Knowledge of the pathway including control mechanisms and genetic mapping will define intermediates important in diseases such as B12 deficiency and acute intermittent porphyria. All of the biosynthetic enzymes necessary for the formation of cobyrinic acid, the simplest B12 analog, will be overexpressed using the sequenced cbi genes of Salmonella typhimurium and the cob genes of Pseudomonas denitrificans and their mechanisms studied by NMR spectroscopy via13C- labeling. Finally, the multi-enzyme synthesis of advanced intermediates and of B12 itself will be addressed.

结合有机化学、分子生物学、酶学和核磁共振 光谱学 尿卟啉原 III（血红素和血红素的前体）生物合成的细节 叶绿素）及其随后转化为维生素 B12（抗恶性贫血因子） 阐明了。包括控制机制和遗传图谱在内的途径知识将定义 对于 B12 缺乏症和急性间歇性卟啉症等疾病很重要的中间体。 形成 Cobyrinic 酸（最简单的 B12）所需的所有生物合成酶 类似物，将使用鼠伤寒沙门氏菌和 cob 的测序 cbi 基因进行过表达 通过13C-核磁共振波谱研究脱氮假单胞菌的基因及其机制 标签。最后，高级中间体和 B12 本身的多酶合成将是 已解决。