Certain acetate-producing anaerobic microorganisms can synthesize biomass via the formation of acetic acid from carbon dioxide. A methyl group and carbon monoxide are derived from carbon dioxide and subsequently condensed with coenzyme A to generate biomass (1–3). On page 567 of this issue, Doukov et al. (4) report the crystal structure of the key enzyme in this process, carbon monoxide dehydrogenase/acetyl– coenzyme A synthase (CODH/ACS). The structure reveals, much to the surprise of many investigators, a trio of transition metals at the active site: iron, nickel, and most unexpectedly, copper. Although clusters with two different transition metals are common, no metalloprotein active site with three different transition metal ions has been reported previously. The discovery also points to a new role for copper in biological systems. In the acetate-production...