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Abstract
Methanol and formate are attractive microbial feedstocks as they can be sustainably
produced from CO2 and renewable energy, are completely miscible, and are easy to store
and transport. Here, we provide a biochemical perspective on microbial growth and
bioproduction using these compounds. We show that anaerobic growth of acetogens on
methanol and formate is more efficient than on H2/CO2 or CO. We analyze the aerobic
C1 assimilation pathways and suggest that new-to-nature routes could outperform their
natural counterparts. We further discuss practical bioprocessing aspects related to
growth on methanol and formate, including feedstock toxicity. While challenges in
realizing sustainable production from methanol and formate still exist, the utilization
of these feedstocks paves the way towards a truly circular carbon economy.