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Publication Abstract from PubMed

Formate can be envisioned at the core of a carbon-neutral bioeconomy, where it is produced from CO(2) 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-gamma-glutamyl phosphate reductase, we demonstrate this phosphate (P(i))-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 P(i) route with a recently developed formaldehyde assimilation pathway to enable C2 compound formation from formate as the sole carbon source in Escherichia coli. The P(i) route therefore offers a potent tool in expanding the landscape of synthetic formate assimilation.

Engineering a new-to-nature cascade for phosphate-dependent formate to formaldehyde conversion in vitro and in vivo.,Nattermann M, Wenk S, Pfister P, He H, Lee SH, Szymanski W, Guntermann N, Zhu F, Nickel L, Wallner C, Zarzycki J, Paczia N, Gaissert N, Francio G, Leitner W, Gonzalez R, Erb TJ Nat Commun. 2023 May 9;14(1):2682. doi: 10.1038/s41467-023-38072-w. PMID:37160875^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.