A synthetic recursive "+1" pathway for carbon chain elongation |
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Authors: | Marcheschi Ryan J Li Han Zhang Kechun Noey Elizabeth L Kim Seonah Chaubey Asha Houk K N Liao James C |
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Institution: | Department of Chemical and Biomolecular Engineering, University of California, Los Angeles, United States. |
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Abstract: | 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-substrate modeling, and protein and metabolic engineering, we have engineered the enzymes involved in leucine biosynthesis for use as a synthetic "+1" 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 "+1" chemistry is a valuable metabolic tool in addition to the "+5" chemistry and "+2" chemistry for the biosynthesis of isoprenoids, fatty acids, or polyketides. |
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