%0 Journal Article %A Marcheschi, Ryan J. %A Li, Han %A Zhang, Kechun %A Noey, Elizabeth L. %A Kim, Seonah %A Chaubey, Asha %A Houk, K. N. %A Liao, James C. %D 2012 %T A Synthetic Recursive “+1” Pathway for Carbon Chain Elongation %U https://acs.figshare.com/articles/journal_contribution/A_Synthetic_Recursive_1_Pathway_for_Carbon_Chain_Elongation/2529082 %R 10.1021/cb200313e.s001 %2 https://ndownloader.figshare.com/files/4172077 %K modeling %K protein %K acid %K recursively catalyze %K Carbon Chain ElongationNature %K isoprenoid %K leucine biosynthesis %K bulk chemicals %K carbon chain %K polyketide %K ketoacid %K carbon chain elongation %K pathway %K QM %K elongation cycles %X 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. %I ACS Publications