Prediction of novel synthetic pathways for the production of desired chemicals.
Prediction of novel synthetic pathways for the production of desired chemicals.
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DOI：
10.1186/1752-0509-4-35
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发表时间：
2010-03-28
影响因子：
--
通讯作者：
Park S
中科院分区：
文献类型：
--
作者：
Cho A;Yun H;Park JH;Lee SY;Park S
已经开发了几种方法来预测合成代谢途径，从而产生所需的化学品。在这些方法中，基于化学结构变化、酶信息和/或反应机理预测新的途径，但是产生大量预测结果的方法难以应用于真实的实验。此外，这些方法中的一些侧重于特定的途径，因此仅限于扩展到整个代谢。在本研究中，我们提出了一个系统框架，采用逆合成模型与优先级评分算法。这种新的策略允许推导出合成所需化学品的新的有前途的途径，以及基于系统数据库中存在的结构变化和反应机制的相关酶的信息。采用Tanimoto系数和基团贡献法的优先级评分算法允许检查结构合格的途径，以识别哪种途径更合适。此外，结合位点共价，途径距离估计和生物体特异性的新概念被考虑到，以确定最佳的合成途径。这些因素的参数可以进化优化时，一个新证明的合成途径注册。作为概念验证，预测了用于生产异丁醇、3-羟基丙酸酯和丁酰辅酶A的新合成途径。该预测显示出高可靠性，其中实验验证的合成途径在所鉴定的候选途径的前0.089%内列出。预计在这项研究中开发的系统框架将是有用的新的代谢途径的硅设计，用于有效生产的化学品，燃料和材料。
There have been several methods developed for the prediction of synthetic metabolic pathways leading to the production of desired chemicals. In these approaches, novel pathways were predicted based on chemical structure changes, enzymatic information, and/or reaction mechanisms, but the approaches generating a huge number of predicted results are difficult to be applied to real experiments. Also, some of these methods focus on specific pathways, and thus are limited to expansion to the whole metabolism. In the present study, we propose a system framework employing a retrosynthesis model with a prioritization scoring algorithm. This new strategy allows deducing the novel promising pathways for the synthesis of a desired chemical together with information on enzymes involved based on structural changes and reaction mechanisms present in the system database. The prioritization scoring algorithm employing Tanimoto coefficient and group contribution method allows examination of structurally qualified pathways to recognize which pathway is more appropriate. In addition, new concepts of binding site covalence, estimation of pathway distance and organism specificity were taken into account to identify the best synthetic pathway. Parameters of these factors can be evolutionarily optimized when a newly proven synthetic pathway is registered. As the proofs of concept, the novel synthetic pathways for the production of isobutanol, 3-hydroxypropionate, and butyryl-CoA were predicted. The prediction shows a high reliability, in which experimentally verified synthetic pathways were listed within the top 0.089% of the identified pathway candidates. It is expected that the system framework developed in this study would be useful for the in silico design of novel metabolic pathways to be employed for the efficient production of chemicals, fuels and materials.
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DOI：
10.1016/s0928-4869(00)00006-9
发表时间：
2000-04-15
期刊：
SIMULATION PRACTICE AND THEORY
影响因子：
--
作者：
Arita, M
通讯作者：
Arita, M
影响因子：
5.6
作者：
Aguilar, D;Aviles, FX;Sternberg, MJE
通讯作者：
Sternberg, MJE
影响因子：
5.6
作者：
Croes, D;Couche, F;van Helden, J
通讯作者：
van Helden, J
影响因子：
4.7
作者：
Li, CH;Henry, CS;Broadbelt, LJ
通讯作者：
Broadbelt, LJ
DOI：
10.1021/ci034018f
发表时间：
2003-05-01
期刊：
JOURNAL OF CHEMICAL INFORMATION AND COMPUTER SCIENCES
影响因子：
--
作者：
Hou, BK;Wackett, LP;Ellis, LBM
通讯作者：
Ellis, LBM