Cross-regulation of amino acid synthesis and anaerobic electron transfer by MetR-mediated methionine signaling

Microorganisms living in nutrient- and energy-limited environments must finely coordinate anabolic and catabolic pathways. However, the molecular mechanisms underlying this balance remain poorly understood. Here, we report a mechanism cross-regulating amino acid biosynthesis and anaerobic respiration in bacterial cells. Using the model bacterium Shewanella oneidensis MR-1, we demonstrated that methionine activates extracellular electron transfer activity at submillimolar concentrations. This regulation is mediated by the transcription factor MetR, a canonical regulator of methionine biosynthesis. Under methionine-limited conditions, MR-1 upregulates methionine biosynthesis genes while repressing genes involved in extracellular electron transfer (metal reduction) and other anaerobic respiratory processes. Conversely, methionine availability relieves this repression, enhancing extracellular electron transfer. Furthermore, the MetR-mediated regulation of extracellular electron transfer was observed in Aeromonas hydrophila . These findings reveal a novel physiological role for MetR, suggesting its involvement in the coordinated energy distribution between anabolic and catabolic pathways.