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ACS Chem Biol. 2012 Apr 20;7(4):689-97. doi: 10.1021/cb200313e. Epub 2012 Feb 3.

A synthetic recursive "+1" pathway for carbon chain elongation.

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Department of Chemical and Biomolecular Engineering, University of California, Los Angeles, United States.


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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