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5.B.5 The Extracellular Metal Oxido-Reductase (EMOR) Family

c-Type cytochromes (c-Cyts) play vital roles in mediating electron transfer (ET) reactions associated with respiration. All c-Cyts possess at least one haem that is covalently bound through amino acid side-chains of the proteins to position and orient the haem moiety and thereby facilitate efficient reactions. The haem moieties are commonly co-ordinated through two thioester bonds to proximal cysteines in the protein, where the signature motif of most c-Cyts is CX2CH (other common motifs include CX3-4CH, CX2CK and A/FX2CH). These motifs with covalently bound haems are the key components used to constitute the haem-containing domains whose functions range from binding of O2 and catalysis to electron transfer and accumulation (Stevens et al., 2004; Rodrigues et al., 2006).

Dissimilatory reduction of metal (e.g. Fe, Mn) (hydr)oxides represents a challenge for microorganisms, as their cell envelopes are impermeable to metal (hydr)oxides that are poorly soluble in water. To overcome this physical barrier, the Gram-negative bacteria Shewanella oneidensis MR-1 and Geobacter sulfurreducens (TC# 5.B.3) have developed electron transfer (ET) strategies that require multihaem c-type cytochromes (c-Cyts) (Shi et al., 2007). In S. oneidensis MR-1, multihaem c-Cyts CymA and MtrA are believed to transfer electrons from the inner membrane quinone/quinol pool through the periplasm to the outer membrane. The type II secretion system translocates decahaem c-Cyts MtrC and OmcA across outer membrane to the surface of bacterial cells where they form a protein complex. The extracellular MtrC and OmcA can directly reduce solid metal (hydr)oxides. Multihaem c-Cyts thus play critical roles in S. oneidensis MR-1- and G. sulfurreducens-mediated dissimilatory reduction of solid metal (hydr)oxides by facilitating ET across the bacterial cell envelope (Shi et al., 2007).

Phototrophic Fe(II)-oxidizing bacteria couple the oxidation of ferrous iron [Fe(II)] to reductive CO2 fixation by using light energy. Rhodopseudomonas palustris TIE-1 has a three-gene operon, designated the pio operon (for phototrophic iron oxidation), that is necessary for phototrophic Fe(II) oxidation. The first gene in the operon, pioA, encodes a c-type cytochrome that is upregulated under Fe(II)-grown conditions. PioA contains a signal sequence and shares homology with MtrA, a decaheme c-type cytochrome from Shewanella oneidensis MR-1 (TC# 5.B.5.1.1). The second gene, pioB, encodes an outer membrane β-barrel protein, a homologue of MtrB from S. oneidensis MR-1. The third gene, pioC, encodes a high potential iron sulfur protein (HiPIP) with a twin-arginine translocation (Tat) signal sequence and is similar to the Fe(II) oxidoreductase (Iro) from Acidithiobacillus ferrooxidans. Like PioA, PioB and PioC appear to be secreted proteins. Deletion of the pio operon results in loss of Fe(II) oxidation activity and growth on Fe(II). Thus, proteins encoded by the pio operon are essential and specific for phototrophic Fe(II) oxidation in R. palustris (Jiao and Newman, 2007).

The autotrophic Sideroxydans lithotrophicus ES-1 can grow by coupling the oxidation of ferrous iron to the reduction of oxygen. Soluble ferrous iron is oxidized at the surface of the cell by an MtoAB porin-cytochrome complex that functions as an electron conduit through the outer membrane. Electrons are then transported to the cytoplasmic membrane where they are used to generate a pmf (for ATP synthesis) and NADH for autotrophic processes such as carbon fixation. As part of the mtoAB gene cluster, S. lithotrophicus also contains the gene mtoD that is proposed to encode a cytochrome c protein. MtoD was chaacteruzed biochemically, biophysicallly, and by x-ray crystallography. MtoD is an 11 kDa monomeric protein containing a single heme that belongs to the class-1 cytochrome c family and had a similar fold to ferricytochrome c552 family.  However the MtoD heme is bis-histidine coordinated and is substantially more exposed than the hemes of other family members.

The electron transfer pathway for the Shewanella metal oxidoreductase is:

quinol (cytoplasmic membrane) → CymA (inner membrane, periplasmic side) → MtrA (periplasm) → MtrB (outer membrane) → OmcA/MtrC complex → Fe3+/Mn3+/4+

References associated with 5.B.5 family:

Barchinger, S.E., S. Pirbadian, C. Sambles, C.S. Baker, K.M. Leung, N.J. Burroughs, M.Y. El-Naggar, and J.H. Golbeck. (2016). Regulation of Gene Expression in Shewanella oneidensis MR-1 during Electron Acceptor Limitation and Bacterial Nanowire Formation. Appl. Environ. Microbiol. 82: 5428-5443. 27342561
Barrozo, A., M.Y. El-Naggar, and A.I. Krylov. (2018). Distinct Electron Conductance Regimes in Bacterial Decaheme Cytochromes. Angew Chem Int Ed Engl 57: 6805-6809. 29663609
Beckwith, C.R., M.J. Edwards, M. Lawes, L. Shi, J.N. Butt, D.J. Richardson, and T.A. Clarke. (2015). Characterization of MtoD from Sideroxydans lithotrophicus: a cytochrome c electron shuttle used in lithoautotrophic growth. Front Microbiol 6: 332. 25972843
Edwards, M.J., G.F. White, C.W. Lockwood, M.C. Lawes, A. Martel, G. Harris, D.J. Scott, D.J. Richardson, J.N. Butt, and T.A. Clarke. (2018). Structural modeling of an outer membrane electron conduit from a metal-reducing bacterium suggests electron transfer via periplasmic redox partners. J. Biol. Chem. 293: 8103-8112. 29636412
Edwards, M.J., G.F. White, J.N. Butt, D.J. Richardson, and T.A. Clarke. (2020). The Crystal Structure of a Biological Insulated Transmembrane Molecular Wire. Cell 181: 665-673.e10. 32289252
Gupta, D., M.C. Sutherland, K. Rengasamy, J.M. Meacham, R.G. Kranz, and A. Bose. (2019). Photoferrotrophs Produce a PioAB Electron Conduit for Extracellular Electron Uptake. mBio 10:. 31690680
Jiao Y., and D.K. Newman. (2007). The pio operon is essential for phototrophic Fe(II) oxidation in Rhodopseudomonas palustris TIE-1.J. Bacteriol. 189: 1765-1773. 17189359
Rabaey, K. and R.A. Rozendal. (2010). Microbial electrosynthesis - revisiting the electrical route for microbial production. Nat. Rev. Microbiol. 8: 706-716. 20844557
Santoro, C., C. Arbizzani, B. Erable, and I. Ieropoulos. (2017). Microbial fuel cells: From fundamentals to applications. A review. J Power Sources 356: 225-244. 28717261
Shi, L., T.C. Squier, J.M. Zachara, and J.K. Fredrickson. (2007). Respiration of metal (hydr)oxides by Shewanella and Geobacter: a key role for multihaem c-type cytochromes. Mol. Microbiol. 65: 12-20. 17581116
Stikane, A., E.T. Hwang, E.V. Ainsworth, S.E.H. Piper, K. Critchley, J.N. Butt, E. Reisner, and L.J.C. Jeuken. (2019). Towards compartmentalized photocatalysis: multihaem proteins as transmembrane molecular electron conduits. Faraday Discuss 215: 26-38. 30969289
White, G.F., Z. Shi, L. Shi, A.C. Dohnalkova, J.K. Fredrickson, J.M. Zachara, J.N. Butt, D.J. Richardson, and T.A. Clarke. (2012). Development of a proteoliposome model to probe transmembrane electron-transfer reactions. Biochem Soc Trans 40: 1257-1260. 23176464
White, G.F., Z. Shi, L. Shi, Z. Wang, A.C. Dohnalkova, M.J. Marshall, J.K. Fredrickson, J.M. Zachara, J.N. Butt, D.J. Richardson, and T.A. Clarke. (2013). Rapid electron exchange between surface-exposed bacterial cytochromes and Fe(III) minerals. Proc. Natl. Acad. Sci. USA 110: 6346-6351. 23538304
Wu, X., L. Zou, Y. Huang, Y. Qiao, Z.E. Long, H. Liu, and C.M. Li. (2018). Shewanella putrefaciens CN32 outer membrane cytochromes MtrC and UndA reduce electron shuttles to produce electricity in microbial fuel cells. Enzyme Microb Technol 115: 23-28. 29859599