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

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，但这些相互作用的进化机制尚不清楚。例如，代谢途径控制着许多细胞过程，但新酶是如何加入到途径中的，以及酶和底物之间的特定相互作用是如何进化的，这些都是未知的。本项目将通过研究皮质类固醇代谢途径的进化来解决这些认识上的空白，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种多样的，并且该途径中的蛋白质在生化上是可处理的。我将结合系统发育学、生物化学、生物物理学和分子生物学来理解生物合成步骤被添加到现有代谢网络中的机制，以及如何产生新的代谢产物的特异性。

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.