The Genome Sequence ofMethanosphaera stadtmanaeReveals Why This Human Intestinal Archaeon Is Restricted to Methanol and H2for Methane Formation and ATP Synthesis

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Abstract
Methanosphaera stadtmanaehas the most restricted energy metabolism of all methanogenic archaea. This human intestinal inhabitant can generate methane only by reduction of methanol with H2and is dependent on acetate as a carbon source. We report here the genome sequence ofM. stadtmanae, which was found to be composed of 1,767,403 bp with an average G+C content of 28% and to harbor only 1,534 protein-encoding sequences (CDS). The genome lacks 37 CDS present in the genomes of all other methanogens. Among these are the CDS for synthesis of molybdopterin and for synthesis of the carbon monoxide dehydrogenase/acetyl-coenzyme A synthase complex, which explains whyM. stadtmanaecannot reduce CO2to methane or oxidize methanol to CO2and why this archaeon is dependent on acetate for biosynthesis of cell components. Four sets ofmtaABCgenes coding for methanol:coenzyme M methyltransferases were found in the genome ofM. stadtmanae. These genes exhibit homology tomtagenes previously identified inMethanosarcinaspecies. TheM. stadtmanaegenome also contains at least 323 CDS not present in the genomes of all other archaea. Seventy-three of these CDS exhibit high levels of homology to CDS in genomes of bacteria and eukaryotes. These 73 CDS include 12 CDS which are unusually long (>2,400 bp) with conspicuous repetitive sequence elements, 13 CDS which exhibit sequence similarity on the protein level to CDS encoding enzymes involved in the biosynthesis of cell surface antigens in bacteria, and 5 CDS which exhibit sequence similarity to the subunits of bacterial type I and III restriction-modification systems.