Synergistic chemo-enzymatic formic acid disproportionation and biomolecular condensates for efficient amino acid production

Formic acid, which can be sustainably produced from CO₂ electroreduction, serves as a renewable liquid C₁ carrier for carbon recycling. However, its biological assimilation is fundamentally constrained by unfavorable thermodynamics and limited metabolic flux. Here, we develop an artificial and efficient pathway to transform formic acid into amino-acid glycine through integrating non-enzymatic formic acid disproportionation with biomolecular condensate-mediated enzyme organization, overcoming these limitations. We first employed amorphous bismuth chromate hydroxide to catalyze formic acid disproportionation, and investigated how amorphous catalyst impacts efficiency, finding that amorphous bismuth chromate hydroxide yield substantially higher catalytic activity and enable the production of formaldehyde at M concentrations alongside CO₂ from formic acid. This chemical step provides a strong thermodynamic driving force for subsequent enzymatic glycine synthesis. Furthermore, we employed liquid-liquid phase separation (LLPS) to create biomolecular condensates, spatially organizing enzymes like natural carboxysomes to enhance catalytic efficiency. This hybrid chemical-biological strategy enables thermodynamically favorable, high-flux glycine production, offering a paradigm for transcending biological thermodynamic constraints through abiotic-biotic synergy coupling with engineered enzyme compartmentalization. • Novel hybrid system directly couples abiotic catalysis with a downstream enzymatic cascade to overcome thermodynamic limits of formic acid utilization. • Amorphous Bi(OH)CrO 4 catalyst catalyse efficient disproportionation of formic acid into formaldehyde at mol/L level. • Biomolecular condensates enhance enzymatic efficiency via synthetic compartmentalization of the cascade. • Synergistic chemo-enzymatic strategy significantly boosts amino acid production yield from formic acid.