Coupling biomanufacturing to decarbonization through hydrogen and formate-driven metabolism

ABSTRACT: Biomanufacturing processes are often constrained by cellular energy requirements that are tightly coupled to carbon metabolism in sugar-based fermentation systems. To address this limitation, we engineered Escherichia coli to use hydrogen gas (H2) and formate (HCOO-) as alternative energy sources, effectively decoupling carbon metabolism from energy generation. This approach enabled the titratable suppression of decarboxylative oxidation of acetate, achieving electron utilization efficiencies of 86.6 ± 1.6% with H2 (via soluble hydrogenase from Cupriavidus necator H16) and 98.4 ± 3.6% with HCOO- (via formate dehydrogenase from Pseudomonas sp. 101). Supplementation with H2 resulted in a significant reduction in CO2 evolution, with decreases of up to 41.0%. Metabolomics experiments suggest that the suppression of carbon loss is mediated by redirecting carbon flux through the glyoxylate shunt, partially bypassing two decarboxylative steps, as evidenced by an accumulation of reduced metabolites in the tricarboxylic acid (TCA) cycle during growth on acetate. We demonstrate the application of this technology by showing up to a 57.6% increase in mevalonate titer in our best-performing strain when treated with HCOO-.

INSTRUMENT(S):

ORGANISM(S): Escherichia Coli Cupriavidus Necator (strain Atcc 17699 / H16 / Dsm 428 / Stanier 337) (ralstonia Eutropha)

SUBMITTER: Christopher Petzold  

LAB HEAD: Christopher J. Petzold

PROVIDER: PXD061595 | Pride | 2026-10-15

REPOSITORIES: Pride