Methanogenic and acetogenic bacteria metabolize carbon monoxide, methanol, formate, hydrogen and carbon dioxide gases and, in the case of certain methanogens, acetate, by single-carbon (C1) biochemical mechanisms. Many of these reactions occur while the C1 compounds are linked to pteridine derivatives and tetrapyrrole coenzymes, including corrinoids, which are used to generate, reduce, or carbonylate methyl groups. Several metalloenzymes, including a nickel-containing carbon monoxide dehydrogenase, are used in both catabolic and anabolic oxidoreductase reactions. We propose biochemical models for coupling carbon and electron flow to energy conservation during growth on C1 compounds based on the carbon flow pathways inherent to acetogenic and methanogenic metabolism. Biological catalysts are therefore available which are comparable to those currently in use in the Monsanto process. The potentials and limitations of developing biotechnology based on these organisms or their enzymes and coenzymes are discussed.