The mechanistic basis for metabolic pathway evolution: the evolution of the corti

代谢途径进化的机制基础：皮质的进化

• 批准号: 8951599
• 负责人: Carrie Frances Olson-Manning
• 金额: $ 5.03万
• 依托单位: UNIVERSITY OF CHICAGO
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-09-01 至 2016-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8951599
• 关键词: Address; Adrenal Cortex Hormones; Aldosterone; Amino Acid Sequence; Animal Model; Animals; Architecture; Biochemical; Biochemical Pathway; Biochemistry; Biological; Biology; Biophysical Process; Biophysics; Cell physiology; Complex; Development; Discipline; Dissection; Endocrinology; Enzymes; Event; Evolution; Gene Duplication; Genes; Genetic; Genomics; Goals; Homeostasis; Hormone Receptor; Hormones; Human; In Vitro; Individual; Mediating; Medical; Metabolic; Metabolic Pathway; Metabolism; Methods; Modeling; Modification; Molecular; Molecular Biology; Mutation; Pathway interactions; Phenotype; Phylogenetic Analysis; Phylogeny; Physiological Processes; Play; Population Genetics; Positioning Attribute; Process; Protein Family; Proteins; Quantitative Genetics; Relative (related person); Rodent; Role; Signal Transduction; Site-Directed Mutagenesis; Specificity; Steroids; Stress; Structure; Study models; Techniques; Vertebrates; base; comparative; enzyme substrate; insight; member; metabolic abnormality assessment; novel; public health relevance; response; salt balance; steroid hormone; structural biology; tool

DESCRIPTION (provided by applicant): While more cellular processes rely on specific interactions, the mechanisms by which these interactions evolve are unknown. Metabolic pathways, for example, control many cellular processes but how new enzymes are added to pathways and how the specific interactions between enzyme and substrate evolve are mostly unknown. This project will address these gaps in understanding by studying the evolution the corticosteroid metabolic pathway, which is responsible for regulating stress, salt balance, metabolism and other important physiological processes. This pathway is diverse among the vertebrates and the proteins in the pathway are biochemically tractable. I will use a combination of phylogenetics, biochemistry, biophysics and molecular biology to understand the mechanisms by which biosynthetic steps are added to existing metabolic networks, and how specificity arises to produce novel metabolic products.

描述（由申请人提供）：虽然更多的细胞过程依赖于特定的相互作用，但这些相互作用演变的机制尚不清楚。例如，代谢途径控制着许多细胞过程，但新的酶是如何加入到代谢途径中的，以及酶和底物之间的特定相互作用是如何演变的，这些都是未知的。该项目将通过研究皮质类固醇代谢途径的演变来解决这些理解上的差距，皮质类固醇代谢途径负责调节应激，盐平衡，代谢和其他重要的生理过程。该途径在脊椎动物中是多样的，并且该途径中的蛋白质在生物化学上是易处理的。我将使用遗传学，生物化学，生物物理学和分子生物学的组合来了解生物合成步骤添加到现有代谢网络的机制，以及特异性如何产生新的代谢产物。

项目成果

Elaboration of the Corticosteroid Synthesis Pathway in Primates through a Multistep Enzyme.

通过多步酶阐述灵长类动物的皮质类固醇合成途径。

• DOI: 10.1093/molbev/msaa080
• 发表时间: 2020
• 期刊: Molecular biology and evolution
• 影响因子: 10.7
• 作者: Olson-Manning,CarrieF