期刊
APPLIED AND ENVIRONMENTAL MICROBIOLOGY
卷 78, 期 22, 页码 7849-7855出版社
AMER SOC MICROBIOLOGY
DOI: 10.1128/AEM.01175-12
关键词
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资金
- Joint BioEnergy Institute [DE-AC02-05CH11231]
- Synthetic Biology Engineering Research Center (SynBERC) through National Science Foundation [BES-0439124]
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.
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