Acetogens are anaerobic bacteria of special interest in fighting environmental and economic impacts caused by massive carbon emissions that pollute our Earth’s atmosphere. These microbes have the unique ability to convert carbon monoxide, carbon dioxide, or methanol into value-added bioproducts. The gas fermentation technology is already at industrial scale and is making use of special acetogens able to produce ethanol natively. Here, we propose a methanol-based bioconversion process using anaerobic methylotrophic acetogens (Eubacterium limosum or Eubacterium callanderi) to produce natively only butyrate or butanol, if genetically modified. Therefore, we depict the crucial fermentation parameters and explain the underlying metabolic pathways to steer these biocatalysts towards sole butyrate production. Additionally, the available genetic toolkits are outlined, and the insights gained via system biology approaches are presented. The concept of the suggested bioprocess is only sustainable if green methanol is used as one-carbon feedstock. The use of black or gray methanol would undoubtedly counteract all efforts towards net-zero CO2 emissions. To meet tightening climate targets and environmental, social, and governance commitments, stakeholders must evaluate a spectrum of low‑carbon technologies. The data presented here indicate that biotechnological fermentations can reduce emissions while remaining commercially competitive, and therefore warrant serious consideration for future industrial deployment and investment.