title: A synthetic recursive "+1" pathway for carbon chain elongation.
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.
authors.affiliation: Department of Chemical and Biomolecular Engineering, University of California, Los Angeles, United States.
authors.forename: Ryan J
authors.initials: RJ
authors.lastname: Marcheschi
authors.forename: Han
authors.initials: H
authors.lastname: Li
authors.forename: Kechun
authors.initials: K
authors.lastname: Zhang
authors.forename: Elizabeth L
authors.initials: EL
authors.lastname: Noey
authors.forename: Seonah
authors.initials: S
authors.lastname: Kim
authors.forename: Asha
authors.initials: A
authors.lastname: Chaubey
authors.forename: K N
authors.initials: KN
authors.lastname: Houk
authors.forename: James C
authors.initials: JC
authors.lastname: Liao
mesh_terms: D002244:Carbon / Q000737:chemistry*; D005227:Fatty Acids / Q000138:chemical synthesis*; D007651:Keto Acids; D060847:Metabolic Engineering; D013729:Terpenes
chemical_list: D005227:Fatty Acids; D007651:Keto Acids; D013729:Terpenes; D002244:Carbon