Microbial metabolism of aliphatic alkenes & epoxides

脂肪族烯烃的微生物代谢

• 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
• 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

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（由申请方提供）：本提案的目的是研究短链烃代谢的微生物途径以及与这些途径相关的酶、辅因子和调控元件的特性。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的影响，是高毒性碳氢化合物氧化产物的性质和命运。例如，短链烯烃如乙烯、丙烯、苯乙烯和异戊二烯（2-甲基丁二烯）的普遍氧化导致环氧化物的产生，环氧化物是高度亲电的烷基化剂。普遍存在的短链饱和烃的氧化包括末端或亚末端羟基化，以分别产生伯醇或仲醇。这些醇的进一步氧化产生有毒的醛（从伯醇）或酮（从仲醇）。环氧化物、醛和酮也作为其他代谢途径的中间体或最终产物以及通过工业过程生产。尽管这些化合物具有毒性，但许多细菌能够直接或间接（即通过将其形成为烃催化剂的中间体）使用脂肪族环氧化物、醛和酮作为碳源和能源来生长。我们实验室的工作揭示了细菌环氧化物和酮代谢中涉及的新的转化、辅因子和酶。具体而言，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基化为β-酮酸以进入中枢代谢。尽管这些转化的表面相似，羧化反应的机理细节是根本不同的。我们打算进一步我们的工作，在细菌的碳氢化合物/环氧化物/酮代谢的羧基化和新的辅因子/酶的中心作用，通过追求这些过程的生化，结构和遗传特性。