To meet the rising global demand for chemicals and fuels, industrial bioproduction requires cheap and sustainable feedstocks. In this context, the one carbon substrate formate represents an ideal mediator between the physicochemical and biological realms. A bioeconomy based on formate would allow to use sustainable platform feedstocks for bioproduction and reduction of CO₂ emissions. Moreover, the easy storage and transportability of formate allows to decouple availability and utilization of renewable energy. However, there are currently no formate-based bioprocesses for “low value-high volume” products.

Supported by the results of our experimental and computational pilot studies, the central aim of FORBIX is to develop an acetogenic platform for microbial formate upgrading into value-added products. To overcome the bioenergetic constraints restricting the acetogenic product spectrum, a direct link of formate utilization to chemiosmotic energy conservation is proposed as a new design principle. We expect that the novel strain design will allow to fully exploit the extremely energy-efficient metabolism of acetogens for formate-based bioproduction. A multidisciplinary approach including metabolic engineering, advanced continuous bioprocessing, multi-omics and computational analyses will yield novel insights into acetogenic metabolism, provide new genetic modules for rational engineering of acetogens, and an extended modeling toolbox for acetogenic metabolism.

If successful, FORBIX will not only implement a new and ground-breaking design principle to improve acetogenic formate metabolism but will also deliver bespoke cell factories and bioprocessing strategies for metabolite synthesis from formate alone and together with gaseous substrates (e.g. H₂ and CO). Ultimately, the results of this project can facilitate establishing industrial bioprocesses rooted in formate utilization and are anticipated to be applicable also to other microbial systems.