Microbial metabolism of aliphatic alkenes & epoxides

脂肪族烯烃的微生物代谢

基本信息

批准号：
7161341
负责人：
Scott A. ENSIGN
金额：
$ 26.34万
依托单位：
UTAH STATE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
1995
资助国家：
美国
起止时间：
1995-04-01 至 2008-11-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7161341
关键词：
ATP Hydrolysis Acetoacetates Acetone Acids Alcohols Aldehyde dehydrogenase (NAD+)Aldehydes Alkenes Alkylating Agents Anabolism Aromatic Hydrocarbons Azotobacter vinelandii Bacteria Bacterial Genome Binding Biochemical Biochemical Genetics Biological Biological Models Biological Process Carbon Catabolism Chromosomes Cleaved cell Coenzyme M Coenzymes Collaborations Discrimination Energy-Generating Resources Enzymes Epoxy Compounds Essential Genes Ethylene Ethylenes Fermentation Funding Genes Genetic Health Homologous Gene Human Hydrocarbons Hydroxylation Isoprene Keto Acids Ketone Bodies Ketones Knock-out Laboratories Localized Manganese Metabolic Metabolic Pathway Metabolism Microbe Molecular Mutagenesis Nature Numbers Operon Organism Oxidoreductase Pathogenicity Pathway interactions Peptic Ulcer Phenotype Physiological Play Process Production Property Pylorus Ralstonia Reaction Regulatory Element Rhodobacter capsulatus Role Sequence Analysis Sinorhizobium meliloti Site Specificity Stomach Carcinoma System Testing Toxic effect Transcription Coactivator USA Georgia Universities Western Asia Georgia Work Xanthobacter autotrophicus Xenobiotic Metabolism acetone carboxylase aldehyde dehydrogenases alkene monooxygenase analog base carboxylate carboxylation cofactor design enzyme pathway follow-up functional genomics interest malignant stomach neoplasm microbial mutant novel oxidation professor propylene

项目摘要

DESCRIPTION (provided by applicant): The objectives of this proposal are to investigate microbial pathways of short-chain hydrocarbon metabolism and the properties of the enzymes, cofactors, and regulatory elements associated with these pathways. While hydrocarbon activation is interesting in its own right, perhaps even more interesting, and with broader implications for human health, are the nature and fate of highly toxic hydrocarbon oxidation products. For example, the ubiquitous oxidation of short-chain alkenes such as ethylene, propylene, styrene and isoprene (2-methybutadiene) results in the production of epoxides, which are highly electrophilic alkylating agents. The ubiquitous oxidation of short-chain saturated hydrocarbons involves either terminal or subterminal hydroxylation to produce primary or secondary alcohols, respectively. The further oxidation of these alcohols produces toxic aldehydes (from primary alcohols) or ketones (from secondary alcohols). Epoxides, aldehydes and ketones are also produced as intermediates or end-products of other metabolic pathways and by industrial processes. In spite of the toxicity of these compounds, a number of bacteria are able to grow using aliphatic epoxides, aldehydes and ketones as carbon and energy sources, either directly or indirectly (i.e. by forming them as intermediates of hydrocarbon catabolism). Work in our laboratory has revealed that novel transformations, cofactors and enzymes are involved in bacterial epoxide and ketone metabolism. Specifically, we discovered CO2-dependent pathways and enzymes for aliphatic epoxide and ketone metabolism, wherein epoxides and ketones are carboxylated to beta-keto acids for entry to central metabolism. In spite of the superficial similarities of these transformations, the mechanistic details of the carboxylation reactions are fundamentally different. We intend to further our work on the central roles of carboxylation and novel cofactors/enzymes in bacterial hydrocarbon/epoxide/ketone metabolism by pursuing the biochemical, structural, and genetic characterization of these processes.

描述（由申请人提供）：本提案的目的是研究短链碳氢化合物代谢的微生物途径以及与这些途径相关的酶、辅因子和调节元件的特性。虽然碳氢化合物活化本身就很有趣，但也许更有趣并且对人类健康具有更广泛影响的是剧毒碳氢化合物氧化产物的性质和命运。例如，乙烯、丙烯、苯乙烯和异戊二烯（2-甲基丁二烯）等短链烯烃的普遍氧化会导致环氧化物的产生，环氧化物是高度亲电的烷基化剂。短链饱和烃的普遍氧化涉及末端或亚末端羟基化，分别产生伯醇或仲醇。这些醇的进一步氧化会产生有毒的醛（来自伯醇）或酮（来自仲醇）。环氧化物、醛和酮也作为其他代谢途径和工业过程的中间产物或最终产物产生。尽管这些化合物具有毒性，但许多细菌能够直接或间接地使用脂肪族环氧化物、醛和酮作为碳和能源（即通过将它们形成碳氢化合物分解代谢的中间体）来生长。我们实验室的工作表明，细菌环氧化物和酮代谢涉及新的转化、辅因子和酶。具体来说，我们发现了脂肪族环氧化物和酮代谢的CO2依赖性途径和酶，其中环氧化物和酮被羧化为β-酮酸以进入中央代谢。尽管这些转化表面上相似，但羧化反应的机制细节却根本不同。我们打算通过研究这些过程的生化、结构和遗传特征，进一步研究羧化和新型辅因子/酶在细菌碳氢化合物/环氧化物/酮代谢中的核心作用。