Exploring the Potential of a Formate-Based Bioeconomy

The Science

Microbial bioproduction uses microorganisms to convert sugars into useful products. However, using sugar as a feedstock could compete with using sugar for food and other agricultural uses. One-carbon (C1) feedstocks are made from carbon dioxide using renewable energy. These feedstocks offer an alternative to sugar. Formate is a promising C1 feedstock. However, there is a lack of effective, fast-growing industrial microbial hosts that can grow on formate. To address this gap, researchers engineered a new strand of E. coli to grow on formate, although it does not do so naturally. They aimed for the strain of E. coli to grow quickly and achieve high-titer bioproduction.

The Impact

Researchers engineered a strain of E. coli to grow on formate at a fast rate and produce a high concentration of bioproducts. The strain effectively produced precursors to biofuels and bioplastics. The team's work demonstrated that scientists can use synthetic microbial hosts that grow on formate as efficient platforms for bioproduction. The researchers also developed an inexpensive method for producing formate from lignin, a polymer found in plant cell walls. Together, these results improve the economic and technical feasibility of developing a healthy bioeconomy.

Summary

Researchers at the Joint BioEnergy Institute sought to address the challenge of slow energy supply for synthetic formatotrophs. (Formatotrophs are microorganisms that can use formate as an energy source.) To do this, they replaced an enzyme in formatotrophic E. coli that converts formate to energy but slows bacterial growth. They swapped it out with a more complex enzyme that uses metals to speed up the reaction. As a result, the strain grew much faster. Its doubling time was approximately 4.5 hours. This time is comparable to the fastest growing natural formatotrophs. Using this strain, they successfully produced mevalonate, a precursor to terpenoids and bioplastics as well as the biofuel isoprenol.

Additionally, the researchers sought to address the high cost of feedstocks like formate. These feedstocks are traditionally made using electrochemistry. They explored an organic waste source, lignin, which could provide formate at a lower cost. Using oxidative degradation, the researchers broke down the lignin into various organic acids, including formate. The researchers used this mixture of organic acids as the energy source for their formatotrophic E. coli strain, which resulted in the production of mevalonate. This suggests a promising method for turning waste lignin into valuable chemicals.

Contact

Jay D. KeaslingJoint BioEnergy [email protected]

Funding

This work was supported by the Joint BioEnergy Institute, which is supported by the U.S. Department of Energy, Office of Science, Biological and Environmental Research Program. Additional support was provided by the DOE Distinguished Scientist Fellow Program, the Philomathia Foundation, the National Institutes of Health, the National Science Foundation, and the VLAG Graduate School.

Publication

Cowan, A.E., Hillers, M., Rainaldi, V., et al. "Fast growth and high-titer bioproduction from renewable formate via metal-dependent formate dehydrogenase in Escherichia coli." Nature Communications (2025). [DOI: 10.1038/s41467-025-61001-y]