Synthetic Pathway for Production of Five-Carbon Alcohols from Isopentenyl Diphosphate
Synthetic Pathway for Production of Five-Carbon Alcohols from Isopentenyl Diphosphate
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DOI：
10.1128/aem.01175-12
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发表时间：
2012-11-01
影响因子：
4.4
通讯作者：
Keasling, Jay D.
中科院分区：
文献类型：
--
作者：
Chou, Howard H.;Keasling, Jay D.
合成生物途径可以促进利用可再生资源生产化学品的新工艺的开发。在描述自然界中代谢途径和酶的进化的模型的基础上，我们开发了一个框架来合理地识别能够在新的底物上催化反应的酶，从而克服了合成生物途径组装中的主要瓶颈之一。我们通过两个新的酶反应将异戊烯基二磷酸转化为3-甲基-3-丁烯醇、3-甲基-2-丁烯醇和3-甲基丁醇，从而验证了该框架。为了克服与共享相同底物的天然途径的竞争，我们设计了两种双功能酶，将代谢流重新定向到合成途径。综上所述，我们的工作展示了一种在细胞中设计新的合成途径的新方法。
Synthetic biological pathways could enhance the development of novel processes to produce chemicals from renewable resources. On the basis of models that describe the evolution of metabolic pathways and enzymes in nature, we developed a framework to rationally identify enzymes able to catalyze reactions on new substrates that overcomes one of the major bottlenecks in the assembly of a synthetic biological pathway. We verified the framework by implementing a pathway with two novel enzymatic reactions to convert isopentenyl diphosphate into 3-methyl-3-butenol, 3-methyl-2-butenol, and 3-methylbutanol. To overcome competition with native pathways that share the same substrate, we engineered two bifunctional enzymes that redirect metabolic flux toward the synthetic pathway. Taken together, our work demonstrates a new approach to the engineering of novel synthetic pathways in the cell.