One-carbon compounds can be made from CO2 to provide renewable microbial feedstocks.
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Methanol and formate have key advantages over gaseous one-carbon feedstocks.
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Growth of acetogens on methanol and formate is promising but underappreciated.
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Coupling methanol assimilation with CO2 fixation boosts yield of oxidized products.
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New-to-nature pathways should outperform natural ones but are yet to be established.
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.
