title: Building carbon-carbon bonds using a biocatalytic methanol condensation cycle.
abstract: Methanol is an important intermediate in the utilization of natural gas for synthesizing other feedstock chemicals. Typically, chemical approaches for building C-C bonds from methanol require high temperature and pressure. Biological conversion of methanol to longer carbon chain compounds is feasible; however, the natural biological pathways for methanol utilization involve carbon dioxide loss or ATP expenditure. Here we demonstrated a biocatalytic pathway, termed the methanol condensation cycle (MCC), by combining the nonoxidative glycolysis with the ribulose monophosphate pathway to convert methanol to higher-chain alcohols or other acetyl-CoA derivatives using enzymatic reactions in a carbon-conserved and ATP-independent system. We investigated the robustness of MCC and identified operational regions. We confirmed that the pathway forms a catalytic cycle through (13)C-carbon labeling. With a cell-free system, we demonstrated the conversion of methanol to ethanol or n-butanol. The high carbon efficiency and low operating temperature are attractive for transforming natural gas-derived methanol to longer-chain liquid fuels and other chemical derivatives.
authors.affiliation: Departments of Chemical and Biomolecular Engineering and Bioengineering, University of California, Los Angeles, CA 90095; and.
authors.forename: Igor W
authors.initials: IW
authors.lastname: Bogorad
authors.affiliation: Departments of Chemical and Biomolecular Engineering and.
authors.forename: Chang-Ting
authors.initials: CT
authors.lastname: Chen
authors.affiliation: Departments of Chemical and Biomolecular Engineering and Bioengineering, University of California, Los Angeles, CA 90095; and.
authors.forename: Matthew K
authors.initials: MK
authors.lastname: Theisen
authors.affiliation: Departments of Chemical and Biomolecular Engineering and.
authors.forename: Tung-Yun
authors.initials: TY
authors.lastname: Wu
authors.affiliation: Departments of Chemical and Biomolecular Engineering and.
authors.forename: Alicia R
authors.initials: AR
authors.lastname: Schlenz
authors.affiliation: Departments of Chemical and Biomolecular Engineering and.
authors.forename: Albert T
authors.initials: AT
authors.lastname: Lam
authors.affiliation: Departments of Chemical and Biomolecular Engineering and Bioengineering, University of California, Los Angeles, CA 90095; and UCLA-DOE Institute for Genomics and Proteomics, University of California, Los Angeles, CA 90095 liaoj@ucla.edu.
authors.forename: James C
authors.initials: JC
authors.lastname: Liao
mesh_terms: D000255:Adenosine Triphosphate / Q000737:chemistry* / Q000378:metabolism; D000440:Butanols / Q000737:chemistry; D002175:Candida / Q000201:enzymology; D002245:Carbon Dioxide / Q000737:chemistry* / Q000378:metabolism; D006019:Glycolysis / Q000502:physiology; D000432:Methanol / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism; D008956:Models, Chemical; D010843:Pichia / Q000201:enzymology; D012441:Saccharomyces cerevisiae / Q000201:enzymology; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry / Q000378:metabolism
chemical_list: D000440:Butanols; D029701:Saccharomyces cerevisiae Proteins; D002245:Carbon Dioxide; D000255:Adenosine Triphosphate; D000432:Methanol
keywords: bio-butanol; bio-ethanol; cell-free synthesis; metabolic engineering; methanol metabolism