The biochemical function of C42 in metal reduction by S. oneidensis is currently unknown. Based on the participation of CXXC motifs in metal binding, redox sensing, and disulfide bond formation (Ritz & Beckwith, 2001; Green & Paget, 2004; Antelmann & Helmann, 2011), potential roles for C42 include the binding of metals or cofactors required MG-132 ic50 for electron transport by the MtrCAB complex, sensing redox conditions via sulfur redox chemistry, or enhancing MtrB interaction with other cysteine-containing metabolites and proteins via heterologous disulfide bond

formation. Current work is focused on examining these possibilities during metal reduction by S. oneidensis. As described above, 20 of the top 21 MtrB

homologs were identified in the genera Ferrimonas, Aeromonas, and Vibrio (Table S3). Although Ferrimonas and Aeromonas species are known to catalyze dissimilatory metal reduction (Knight & Blakemore, 1998; Nakagawa et al., 2006; Nolan et al., 2010), the dissimilatory metal reduction capability of Vibrios is not well CDK activity studied. The ability to predict dissimilatory metal reduction by a γ-proteobacterium with unknown metal reduction capability was tested with V. parahaemolyticus, a pathogen whose genome encodes an MtrB homolog with an N-terminal CXXC motif. A CSEC motif was identified in the N-terminus of the V. parahaemolyticus MtrB homolog VP1218 (87QD1_VIBPA; Table S3). Subsequent anaerobic incubations demonstrated that V. parahaemolyticus reduced Fe(III) and Mn(IV) as terminal electron acceptors (Fig. 3), while V. harveyi, a Vibrio control strain lacking the MtrB homolog, was deficient in Fe(III) and Mn(IV) reduction activity (Fig. 3). Results of the present study indicate that MtrB homologs of metal-reducing γ-proteobacteria contain an N-terminal CXXC motif that is missing from the MtrB homologs of Acidobacteria and NC10 group strains, nonmetal-reducing γ-proteobacteria, and all α-, β-, and δ-proteobacteria, Glycogen branching enzyme including those catalyzing dissimilatory

metal reduction or oxidation reactions. The N-terminal CXXC motif of MtrB is required for dissimilatory metal reduction by the representative metal-reducing γ-proteobacterium S. oneidensis, and the ability to predict dissimilatory metal reduction by a γ-proteobacterium with unknown metal reduction capability was confirmed with V. parahaemolyticus, a pathogen whose genome encodes an MtrB homolog with an N-terminal CXXC motif. MtrB homologs with N-terminal CXXC motifs may thus represent a molecular signature unique to metal-reducing members of the γ-proteobacteria, with the potential for further development as a biomarker for tracking the presence and activity of metal-reducing γ-proteobacteria in natural and engineered systems. This work was supported by the National Science Foundation, the Department of Energy, and the Public Service Department of Malaysia.