Manganese Biomineralization by a Multicopper Oxidase Protein Complex

In oxic environments, the stable form of manganese is an insoluble MnO2 mineral. However, the uncatalyzed oxidation of soluble Mn(II) is very slow. Consequently, this oxidation, a key part of the global manganese cycle, is largely under biological control, being carried out by bacteria and fungi. Dormant spores of many Bacillus species employ multicopper oxidase enzymes (MCOs) that use oxygen directly to oxidize Mn(II) and form MnO2 minerals. This presents a biochemical conundrum, because MCOs work through single electron transfers from their substrates, whereas conversion of Mn(II) to MnO2 is a 2-electron oxidation, involving one-electron steps with high kinetic barriers due to high reduction potentials. How is this accomplished? Expression and purification of the first bacterial manganese oxidizing MCO complex Mnx created a new chapter in the field of inorganic biochemistry: protein-controlled manganese biomineralization. This review documents the history of genetic studies in Bacillus sp. that led to production of the enzymatic complex Mnx responsible for Mn biomineralization. Biochemical and cryoelectron microscopy structural studies then showed how Mnx has solved the problem of high kinetic barriers to Mn oxidation by exploiting the stabilizing effect of hydroxo- and oxo-bridging in binuclear Mn complexes in all three oxidation states, II, III, and IV. We offer an outlook for future directions of manganese biomineralization research, connecting it to broader quests in the fields of geochemistry and geomicrobiology.