A Synthetic Recursive 鈥?1鈥?Pathway for Carbon Chain Elongation

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• 作者：Ryan J. Marcheschi ; Han Li ; Kechun Zhang ; Elizabeth L. Noey ; Seonah Kim ; Asha Chaubey ; K. N. Houk ; James C. Liao
• 刊名：ACS Chemical Biology
• 出版年：2012
• 出版时间：April 20, 2012
• 年：2012
• 卷：7
• 期：4
• 页码：689-697
• 全文大小：394K
• 年卷期：v.7,no.4(April 20, 2012)
• ISSN：1554-8937

文摘

Nature uses four methods of carbon chain elongation for the production of 2-ketoacids, fatty acids, polyketides, and isoprenoids. Using a combination of quantum mechanical (QM) modeling, protein鈥搒ubstrate modeling, and protein and metabolic engineering, we have engineered the enzymes involved in leucine biosynthesis for use as a synthetic 鈥?1鈥?recursive metabolic pathway to extend the carbon chain of 2-ketoacids. This modified pathway preferentially selects longer-chain substrates for catalysis, as compared to the non-recursive natural pathway, and can recursively catalyze five elongation cycles to synthesize bulk chemicals, such as 1-heptanol, 1-octanol, and phenylpropanol directly from glucose. The 鈥?1鈥?chemistry is a valuable metabolic tool in addition to the 鈥?5鈥?chemistry and 鈥?2鈥?chemistry for the biosynthesis of isoprenoids, fatty acids, or polyketides.