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

Ryan J. Marcheschi, Han Li, Kechun Zhang, Elizabeth L. Noey, Seonah Kim, Asha Chaubey, K. N. Houk, James C. Liao

Research output: Contribution to journalArticlepeer-review

83 Scopus citations

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 "+" chemistry is a valuable metabolic tool in addition to the "+5" chemistry and "+2" chemistry for the biosynthesis of isoprenoids, fatty acids, or polyketides.

Original languageEnglish (US)
Pages (from-to)689-697
Number of pages9
JournalACS Chemical Biology
Volume7
Issue number4
DOIs
StatePublished - Apr 20 2012

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