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ENZYMES OF AROMATIC ACID METABOLISM

芳香酸代谢酶

基本信息

批准号：
3292375
负责人：
John W Kozarich
金额：
$ 9.14万
依托单位：
UNIV OF MARYLAND, COLLEGE PARK
依托单位国家：
美国
项目类别：
财政年份：
1986
资助国家：
美国
起止时间：
1986-07-01 至 1994-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/3292375
关键词：
Fungi Imperfecti Pseudomonas cyclic acid decarboxylases detoxification enol enzyme mechanism enzyme substrate enzymes halocarbon compound hydrolase nuclear magnetic resonance spectroscopy stereochemistry ultraviolet spectrometry

项目摘要

This renewal application seeks continued support for our investigations of the chemistry and enzymology of the enzymes of the beta-ketoadipate pathway. During the current funding period we have made considerable progress on nearly all of our initially stated goals. In addition, our mechanistic and stereochemical findings have revealed some unusual interrelationships among a number of enzymes in this pathway and have suggested that some of these enzymes may have evolved to accommodate preferred mechanistic pathways and not on the basis of structural features of common substrate classes. During the next funding period, we have put together a multidisciplinary program which includes a microbiologist (L.N. Ornston) and two crystallographers (A. Goldman and D.A. Ollis). We intend to interface our chemical and enzymological studies with the genetic and structural studies of these research groups. We are also moving our work aggressively into the area of the metabolism of halogenated aromatic compounds by a variety of enzymes in the beta-ketoadipate pathway. Specifically, we will be investigating the following: I. Chemical synthesis of disubstituted muconate derivatives. II. Chemical lactonization of substituted muconates. III. Studies on 3-carboxymuconate cyloisomerase (CMLE) from P. putida. IV. Studies on muconolactone delta-isomerase and 4-carboxymuconolactone decarboxylase. V. Studies on muconate cyloisomerases from P. sp. B13 and T. cutaneum. In light of the increasing importance of these metabolic pathways to environmental chemistry, we believe that the new chemistry and enzymology uncovered will be of great value to microbiologists, chemists and biochemists concerned with the detoxification of polyhalogenated aromatics.

这一更新申请寻求继续支持我们的调查 β-酮己二酸的化学和酶学通路在目前的融资期内，几乎所有我们最初提出的目标都取得了进展。另外我们机械和立体化学的发现揭示了一些不寻常的在这一途径中的许多酶之间的相互关系，这表明，这些酶中的一些可能已经进化到适应优选的机制途径，而不是基于结构常见基材类别的特征。在下一个资助期内，我们已经建立了一个多学科的该计划包括微生物学家（L.N. Ornston）和两个晶体学家（A. Goldman和D.A. Ollis）。我们打算与我们的化学和酶学研究，这些研究小组的研究。我们也在把工作积极进入卤代芳香族化合物代谢领域，通过β-酮己二酸途径中的多种酶来合成化合物。具体而言，我们将调查以下内容： I. 二取代粘康酸酯衍生物的化学合成。二. 取代粘康酸酯的化学内酯化。三. 恶臭假单胞菌3-羧基粘康酸环异构酶的研究四. 粘康酸内酯δ-异构酶和4-羧基粘康酸内酯的研究脱羧酶诉 P.sp.B13和T.皮肤。鉴于这些代谢途径对环境化学，我们相信，新的化学和酶学的发现将对微生物学家、化学家、和生物化学家关注的多卤化解毒芳香剂