Metabolic engineering of microorganisms for the valorization of C₂ feedstocks

This review summarizes recent advances in the metabolic engineering of microorganisms for the valorization of C₂ feedstocks into high-value chemicals and materials. We first discuss native and engineered C₂ assimilation pathways, including reverse β-oxidation, aldol-condensation-based carbon extension, and thiamine pyrophosphate-dependent modules, highlighting representative strain designs in Escherichia coli, Pseudomonas spp., and photosynthetic hosts. We then examine C₁-to-C₂ platform strategies that couple acetogens or gas-fermenting microbes with C₂-assimilating production strains. Finally, we outline the rapidly growing toolbox of non-natural and computationally designed pathways that rewire carbon flux with minimal loss. Particular emphasis is placed on the integration of synthetic biology, enzyme engineering, genome-scale metabolic models, and artificial intelligence-driven design for building next-generation, electrified, and digitally guided C₂ biorefineries. These advances are positioning C₂-based biomanufacturing as a key pillar of low-carbon chemical production.