Carbon capture and utilization is considered a promising approach for introducing CO2 into the chemical value, especially in combination with bioenergy applications (BECCU). We demonstrate here the catalytic hydrogenation of...

Joining bio- and chemo-catalysis: whole-cell fermentation of glucose to ethanol is combined with in situ hydrogenation of the by-product CO2 to formic acid using a tailored Ru-catalyst in a water–tetradecane biphasic system.

Formate can be envisioned at the core of a carbon-neutral bioeconomy, where it is produced from CO2 by (electro-)chemical means and converted into value-added products by enzymatic cascades or engineered microbes. A key step in expanding synthetic formate assimilation is its thermodynamically challenging reduction to formaldehyde. Here, we develop a two-enzyme route in which formate is activated to formyl phosphate and subsequently reduced to formaldehyde. Exploiting the promiscuity of acetate kinase and N-acetyl-γ-glutamyl phosphate reductase, we demonstrate this phosphate (Pi)-based route in vitro and in vivo. We further engineer a formyl phosphate reductase variant with improved formyl phosphate conversion in vivo by suppressing cross-talk with native metabolism and interface the Pi route with a recently developed formaldehyde assimilation pathway to enable C2 compound formation from formate as the sole carbon source in Escherichia coli. The Pi route therefore offers a potent tool in expanding the landscape of synthetic formate assimilation.

In recent years, it was shown that itaconic acid can be produced from glucose with Ustilago strains at up to maximum theoretical yield. The use of acetate and formate as co-feedstocks can boost the efficiency of itaconate production with Ustilaginaceae wild-type strains by reducing the glucose amount and thus the agricultural land required for the biotechnological production of this chemical. Metabolically engineered strains (U. cynodontis ∆fuz7 ∆cyp3 ↑ Pria1 and U. cynodontis ∆fuz7 ∆cyp3 PetefmttA ↑ Pria1) were applied in itaconate production, obtaining a titer of 56.1 g L−1 and a yield of 0.55 gitaconate per gsubstrate. Both improved titer and yield (increase of 5.2 g L−1 and 0.04 gitaconate per gsubstrate, respectively) were achieved when using sodium formate as an auxiliary substrate. By applying the design-of-experiments (DoE) methodology, cultivation parameters (glucose, sodium formate and ammonium chloride concentrations) were optimized, resulting in two empirical models predicting itaconate titer and yield for U. cynodontis ∆fuz7 ∆cyp3 PetefmttA ↑ Pria1. Thereby, an almost doubled itaconate titer of 138 g L−1 was obtained and a yield of 0.62 gitaconate per gsubstrate was reached during confirmation experiments corresponding to 86% of the theoretical maximum. In order to close the carbon cycle by production of the co-feed via a “power-to-X” route, the biphasic Ru-catalysed hydrogenation of CO2 to formate could be integrated into the bioprocess directly using the obtained aqueous solution of formates as co-feedstock without any purification steps, demonstrating the (bio)compatibility of the two processes.

All catalysts have unique abilities. This is especially true for microbial, enzymatic, and organometallic catalysis, which are often seen as competitive approaches preventing the exploitation of their complementarity. An increasing number of examples show, how using the complete catalytic spectrum can open roads from new substrates to new products. C1‐compounds such as formate, formaldehyde, methanol, or methane from CO2 in combination with green H2 are likely to be future sources of carbon feedstock. This short review highlights how combinations of different catalyst types can facilitate integrated reaction sequences with biogenic substrates to form “bio‐hybrid” fuels and products.