Acyl-CoA carboxylases of Streptomyces coelicolor: its c*

天蓝色链霉菌的酰基辅酶A羧化酶：其c*

• 批准号: 6442018
• 负责人: CHAITAN KHOSLA
• 金额: $ 3.77万
• 依托单位: STANFORD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-12-14 至 2004-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6442018
• 关键词: Actinomyces; Escherichia coli; South America; Streptomyces; acetyl coA carboxylase; acyl coA; antibiotics; bacterial proteins; chemical kinetics; cooperative study; densitometry; drug design /synthesis /production; enzyme biosynthesis; enzyme complex; enzyme structure; enzyme substrate complex; erythromycin; polyketide synthase; stoichiometry

DESCRIPTION (provided by applicant) Acyl-CoA carboxylases are enzyme complexes with the ability to carboxylate short-chain acyl-CoAs such as acetyl-, propionyl- and butyryl-CoA to yield malonyl-, methylmalonyl- and ethylmalonyl-CoA. These enzyme complexes have been mostly described in actinomycetes, although no information related with their specific physiological role or with their biochemical properties is still available. The broad objective of the present project is the biochemical characterization of two acyl-CoA carboxylases of Streptomyces coelicolor. These studies will be mainly directed to identify the source of the substrate specificity/tolerance of these complexes and also to dissect the role of a new characterized subunit in the reaction mechanism of these enzymes. The broad goal of the parent grant is to understand the tolerance and specificity of Polyketide Synthetases (PKSs), which are large multienzyme systems that are responsible for the stepwise biosynthesis of complex natural products from simple 2-, 3-, and 4-carbon building blocks such as acetyl-, propionyl-, butyryl-CoA and their activated derivatives malonyl- methylmalonyl- and ethylmalonyl-Co. The knowledge gained on the biochemistry of the acyl-CoA carboxylases and PKS will be used to try to overexpress both systems in Escherichia coli in order to optimize the production of polyketide compounds in this versatile bacterium.

描述（由申请人提供） 酰基-COA羧化酶是具有羧酸盐的酶复合物 短链酰基-COA，例如乙酰基，丙酰基和丁酰基-COA，以产生 malonyl-，甲基丙二酰基和乙基甲基甲酸-COA。这些酶复合物已经 尽管没有与它们的信息有关 特定的生理作用或其生化特性仍然是 可用的。 本项目的广泛目标是生化特征 两种链霉菌卵石的酰基-COA羧化酶。这些研究将是 主要指示识别底物特异性/公差的来源 在这些复合物中，还剖析了新特征亚基的作用 在这些酶的反应机理中。 父母赠款的广泛目标是了解容忍度和 聚酮化合物合成酶（PKSS）的特异性是大型多元素 负责复杂自然的逐步生物合成的系统 来自简单2、3和4-碳构建块的产品，例如乙酰基 - 丙基，丁酰基-COA及其活化的衍生物丙二酰甲基氨基甲硅烷基 - 和乙基甲基-CO。关于酰基-COA的生物化学的知识 羧酸酶和PK将用于尝试过表达这两个系统 大肠杆菌以优化聚酮化合物的产生 这种多功能细菌。