Novel outlook in engineering synthetic methylotrophs and formatotrophs: a course for advancing C1-based chemicals production

The world is at a critical stage to switch from fossil and agriculture feedstocks with sustainable alternatives for the production of biobased chemicals of everyday use. This has spurred interest in using carbon one compounds; methanol and formate as a substrate or cosubstrate for microbial-based production. However, considering that native methylotrophs and formatotrophs utilize methanol and formate respectively, their capabilities to efficiently produce high value-added chemicals are limited. Therefore, shifting from these native C1 microbes to metabolically engineered non-native C1 model strains has attracted increasing attention thanks to many advantages such as the availability of well-established tools and strategies for metabolic engineering, and in addition to its high cell growth rate. Herein, we discussed recent trends in developing synthetic methylotrophs and formatotrophs for methanol and formate-based biomanufacturing. Finally, we highlighted barriers and provided broad prospects on possible avenues for optimizing synthetic methylotrophic and formatotrophic strains with respect to the recent advances in biology.