Methanogenesis from the antidiabetic drug metformin

Pharmaceutical compounds are widespread in anoxic environments, yet their direct utilization by methanogens has not been demonstrated. We show that the antidiabetic drug metformin can serve as a substrate for methane production by the obligate methylotroph Methermicoccus shengliensis, representing the first reported case of methanogenesis from pharmaceuticals. Long-term incubations revealed methane production concomitant with 30% metformin consumption over 71 days, accompanied by 7% incorporation of ¹³C-labeled CO₂ into methane, which is lower than the ~30% reported for M. shengliensis during growth on methoxylated coal compounds (1). No methane production or degradation was observed for naproxen, an anti-inflammatory drug, despite its O-methoxy group being structurally similar to methoxylated coal compounds.

Proteomic analyses revealed substrate-specific differences between metformin- and methanol-grown cultures (reference substrate), including overexpression of dimethylamine-methyltransferases and changes in the expression of energy metabolism proteins. A strong stress response was observed, characterized by overexpression of proteins involved in metabolic maintenance and stress mitigation. Several upregulated proteins, along with those associated with potential substrate degradation or transport, were located within predicted horizontally transferred genomic regions.

This study expands the known substrate range of methylotrophic methanogens and identifies pharmaceuticals as a previously unrecognized contributor to anaerobic methane production, with potential implications for subsurface carbon cycling in contaminated environments.

 

(1) D. Mayumi et al., Methane production from coal by a single methanogen. Science 354, 222-225 (2016).