Computational discovery of biochemical routes to specialty chemicals
Computational discovery of biochemical routes to specialty chemicals
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DOI：
10.1016/j.ces.2004.09.021
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发表时间：
2004-11-01
影响因子：
4.7
通讯作者：
Broadbelt, LJ
中科院分区：
文献类型：
--
作者：
Li, CH;Henry, CS;Broadbelt, LJ
已经开发了一个计算框架，用于在给定输入底物和酶催化反应知识的情况下构建和评估代谢途径。该框架的应用为生物系统中已知存在的化学物质和生物系统中新颖的化学物质创造了新的和现有的途径。在本申请中，我们重点关注7-羧基吲哚的生物合成途径，7-羧基吲哚是一种目前通过有机合成生产的特种化学品，使用分支酸作为起始化合物，以及从分支酸到色氨酸的生物合成途径固有的酶作用。利用图论及其相关算法来表示分子并执行酶催化反应。通过重复应用代表反应物及其后代感兴趣的酶促反应的一组算子，自动生成反应路径。根据酶分类系统（EC i.j.k.l）的四位变换，引入广义酶函数的概念，定义为三级酶函数（EC i.j.k）。这一概念将酶催化反应映射到官能团的转化，并能够产生新的物种和途径。使用“即时”基团贡献方法计算热力学性质，以便对新途径的相对可行性进行评估。 (C) 2004 Elsevier Ltd. 保留所有权利。
A computational framework has been developed for the construction and evaluation of metabolic pathways given input substrates and knowledge of enzyme-catalyzed reactions. Application of the framework creates new and existing routes to both chemicals known to exist in biological systems and chemicals novel to biological systems. In the present application, we focus on biosynthetic routes to 7-carboxyindole, a specialty chemical currently produced by organic synthesis, using chorismate as a starting compound and the enzyme actions native to the biosynthetic route from chorismate to tryptophyan. Graph theory and its associated algorithms are exploited to represent molecules and perform enzyme-catalyzed reactions. Through repetitive application of the set of operators representing the enzymatic reactions of interest to the reactants and their progeny, reaction pathways are generated automatically. The concept of generalized enzyme function is introduced and defined as the third-level enzyme function (EC i.j.k) according to the four-digit transformations of the enzyme classification system (EC i.j.k.l). This concept maps enzyme-catalyzed reactions to transformations of functional groups and enables the generation of novel species and pathways. Thermodynamic properties are calculated using a group contribution method "on-the-fly" in order to provide one assessment of the relative feasibility of the novel pathways. (C) 2004 Elsevier Ltd. All rights reserved.