Engineering bacterial morphology through MreB remodeling enhances one-carbon metabolism for sustainable bioproduction

The actin-like cytoskeletal protein MreB controls bacterial cell morphology, yet whether engineered modulation of MreB-associated architecture can improve microbial metabolism remains largely unexplored. Here, we established a chemical-genetic platform in Escherichia coli combining an engineered MreB variant (A53R) that remodels cellular morphology with A22-mediated perturbation of MreB dynamics. MreB(A53R) reshaped cell morphology and engaged an RpoE-Cra-GadE regulatory network associated with cellular adaptation, which remodeled electron transport, redirected carbon flux toward NADPH-generating pathways, and reduced intracellular reactive oxygen species (ROS). Consequently, engineered strains exhibited enhanced formaldehyde tolerance and efficient assimilation of methanol and other C1 substrates. Acute A22 treatment recapitulated the morphological alteration but failed to induce metabolic rewiring, revealing a two-stage adaptive response involving immediate physical adaptation associated with cell envelope reinforcement and long-term transcription-dependent metabolic adaptation to persistent morphological remodeling. The analogous V45R mutation in the native methylotroph Bacillus methanolicus partially recapitulated the improved C1 utilization phenotype, supporting the transferability of MreB-based morphological engineering. Collectively, these findings establish MreB-mediated morphological engineering as a strategy to couple cellular architecture with central carbon and redox metabolism and provide a framework for engineering robust microbial chassis for C1 bioconversion.