PORPHYRIN AND CORRINOID BIOSYNTHESIS

卟啉和类咕啉生物合成

基本信息

批准号：
7340492
负责人：
Frank M. Raushel
金额：
$ 51.97万
依托单位：
TEXAS A&M UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
1982
资助国家：
美国
起止时间：
1982-06-01 至 2010-01-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7340492
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

项目摘要

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NMR 光谱法尿素原III的生物合成的细节（血红素和血红素的前身叶绿素及其随后转化为维生素B12，抗可治化的贫血因子将是阐明。了解包括控制机制和遗传图的途径的知识将定义中间体在B12缺乏症和急性间歇性卟啉症等疾病中很重要。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基因过表达假单胞菌的基因denitrificans及其通过NMR光谱via13c-研究的机制标签。最后，高级中间体和B12本身的多酶合成将是解决。

项目成果

期刊论文数量（14）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Mutagenesis identifies a conserved tyrosine residue important for the activity of uroporphyrinogen III synthase from Anacystis nidulans.

诱变鉴定了对来自 Anacystis nidulans 的尿卟啉原 III 合酶活性很重要的保守酪氨酸残基。

DOI：
10.1016/s0014-5793(02)03056-9
发表时间：
2002
期刊：
FEBS letters
影响因子：
3.5
作者：
Roessner,CharlesA;Ponnamperuma,Krishan;Scott,AI
通讯作者：
Scott,AI

Site-directed mutagenesis and high-resolution NMR spectroscopy of the active site of porphobilinogen deaminase.

胆色素原脱氨酶活性位点的定点诱变和高分辨率核磁共振波谱。

DOI：
10.1021/bi00421a002
发表时间：
1988
期刊：
Biochemistry
影响因子：
2.9
作者：
Scott,AI;Roessner,CA;Stolowich,NJ;Karuso,P;Williams,HJ;Grant,SK;Gonzalez,MD;Hoshino,T
通讯作者：
Hoshino,T

Analytical and preparative separation of uroporphyrin I and III by high-performance liquid chromatography.

通过高效液相色谱法对尿卟啉 I 和 III 进行分析和制备分离。