Building carbon–carbon bonds using a biocatalytic methanol condensation cycle

Significance 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.