JHI [48], reveal NSC 125973 that their gene content is largely comparable, particularly AbM4 and JHI (Figure 4). This suggests that the central metabolism and the methanogenesis pathway of these strains are similar. Methanobrevibacter sp. AbM4 is a hydrogenotrophic methanogen and the genes involved in the methanogenesis pathway, and associated functions are shown in Figure 5. The presence or absence of these genes is indicated within complete genomes of gut methanogens of the order Methanobacteriales. The methane formation pathway in AbM4 is very similar to that of M1 and each of the 7 enzymatic steps expected for the reduction of CO2 (or formate) through to methane using H2 is present.

AbM4 and M1 are distinguished from the human gut methanogens, Methanobrevibacter smithii PS [49] and Methanosphaera stadtmanae MCB-3 [50], by the absence of the methanol:cobalamin methyltransferase genes (mtaABC) which mediate methanol utilization in these organisms. Hydrogenotrophic methanogens generally encode a methyl coenzyme reductase II (mcrII or mrt), an isoenzyme of the methyl CoM reductase I (mcrI) enzyme which is differentially regulated during growth [52] to mediate methane formation at high partial pressures of H2. Like M1, AbM4 contains only the McrI system for the final methyl-CoM reduction step in methanogenesis. PS contains both the McrI and II systems whereas MCB-3 contains only the McrII system. In the rumen, methanogens depend on fermentative microbes to supply H2, usually at very low concentrations, and AbM4 and M1 appear to have adapted their lifestyle for growth at low levels of H2 using the McrI system only.

Comparable with M1, AbM4 contains several genes (two NADPH-dependent F420 dehydrogenase genes and three alcohol dehydrogenase genes) which may support growth on alcohols such as methanol and ethanol [2,53]. Figure 4 Venn diagram displaying gene conservation between the orfeome of Methanobrevibacter ruminantium M1, Methanobrevibacter sp. JHI, and Methanobrevibacter sp. AbM4. Analysis performed using GAMOLA [31] and OrthoMCL, Version 1.4 [51]. Numbers within circles … Figure 5 Comparison of predicted coding DNA sequence (CDS) content for methanogenesis associated functions from completed methanogen genomes found in mammalian gut environments. CDSs are arranged as methanogenesis-associated (A), methanogenesis (B) or membrane …

Genes unique to AbM4 as compared with other rumen methanogens (Figure. 4) and with an annotated function are enriched for type I and type II restriction-modification systems (Table 6). Compared to M1, AbM4 does not harbor a prophage but does contain a large (~16 kb) CRISPR region (sequence Anacetrapib coordinates 134,105-150,352 bp). AbM4 has a greatly reduced complement of predicted adhesin-like proteins when compared to M1 (29 versus 105) and it lacks non-ribosomal peptide synthase genes that have been observed in M1.