초록
<P><B>Significance</B></P><P>With the recent discoveries of large reserves of natural gas, the efficient utilization of one-carbon compounds for chemical synthesis would reduce the raw material cost for the petroleum-based chemical industry. Methanol is produced industrially from methane and is a feedstock chemical for the synthesis of higher carbon compounds. However, current chemical synthesis of higher carbon compounds from methanol requires high temperature and pressure. Natural biological pathways for methanol utilization are carbon and ATP inefficient. Here we constructed a synthetic biocatalytic pathway that allows the efficient conversion of methanol to higher-chain alcohols or other higher carbon compounds without carbon loss or ATP expenditure. The high carbon efficiency and favorable operating conditions are attractive for industrial applications.</P><P>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 <SUP>13</SUP>C-carbon labeling. With a cell-free system, we demonstrated the conversion of methanol to ethanol or <I>n</I>-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.</P>