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Methanol has become an attractive substrate for biotechnological applications due to its abundance and low-price. Chemicals production from methanol could alleviate the environmental concerns, costs, and foreign dependency associated with the use of petroleum feedstock. Recently, a growing fraction of research has focused on metabolites production using methanol as sole carbon and energy source or as co-substrate with carbohydrates by native or synthetic methylotrophs. In this review, we summarized the recent significant progress in native and synthetic methylotrophs and their application for methanol bioconversion into various products. Moreover, strategies for improvement of methanol metabolism and new perspectives on the generation of desired products from methanol were also discussed, which will benefit for the development of a methanol-based economy.

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Methanol is increasingly becoming an attractive carbon feedstock for the production of various biochemicals due to its high abundance and low price. In this study, when methanol assimilation module was introduced into succinic acid producing Escherichia coli by employing the NAD-dependent methanol dehydrogenase from Bacillus methanolicus and ribulose monophosphate pathway from different donor organisms, succinic acid yield was increased from 0.91 ± 0.08 g/g to 0.98 ± 0.11 g/g with methanol as an auxiliary substrate under the anaerobic fermentation. Further 13 C-labeling experiments showed that the recombinant strain successfully converted methanol into succinic acid, as the carbon atom of carboxyl group in succinic acid was labeled by 13 C. It was found that the NADH generated by methanol oxidation would benefit succinate production, as the NADH/NAD + ratio in vivo was decreased from 0.67 to 0.45 in the engineered strain, indicating that the efficiency of succinic acid synthesis was significantly improved when driven by methanol. This study represents a successful case for the development of reducing chemical production using methanol as an auxiliary substrate.

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