An Ammonia-Metabolizing Enzyme from the Human Archaeon Methanobrevibacter Smithii Might Represent a Missing Link in the Evolution of Carbamoyl Phosphate Synthetases

ABSTRACT

Methanobrevibacter smithii, the major archaeon in human gut, possesses two putative carbamoyl phosphate synthetases (CPS) for catalyzing the precursor of arginine and pyrimidines biosynthetic pathways. These enzymes represent a unique CPS system involved in ammonium assimilation, and appear to be essential for controlling this process involved in host obesity mechanisms. The M. smithii CPSs are encoded by a carA gene, coding for glutaminase subunit (GLN), and three carB genes coding for synthetase subunits (SYN). These SYN are very different in size, SYN1of 1058 residues, and two small size subunits of 391 residues (SYN2) and 367 residues (SYN3), respectively. These hypothetical polypeptides show conserved active site aminoacids. Remarkably, M. smithii SYN2 and SYN3 appear to be the smallest CPS subunits identified so far that might reconstitute the “large” synthetase of most CPSs. The presence of such small CPS SYN in some methanogenic archaea might indicate a specific pattern for these ammonia-consuming enzymes in this class of microooganisms, and in M. smithii it might constitute a putative target for regulation of obesity-determining processes. Corroboration of the structural and functional properties of these archaeal CPSs might lead to identify one of the ancestral forms of this class of enzymes.

Keywords:

• archaea
• carbamoyl phosphate synthetase
• ammonia
• evolution
• gut