The evolution of acetyl-CoA synthase

Acetyl-coenzyme A synthases (ACS) are Ni-Fe-S containing enzymes found in a rchaea and bacteria. They are divisible into 4 classes. Class I ACS's catal yze the synthesis of acetyl-CoA from CO2 + 2e(-), CoA, and a methyl group, and contain 5 types of subunits (alpha, beta, gamma, delta, and epsilon). C lass II enzymes catalyze essentially the reverse reaction and have similar subunit composition. Class III ACS's catalyze the same reaction as Class I enzymes, but use pyruvate as a source of CO2 and 2e(-), and are composed of 2 autonomous proteins, an alpha (2)beta (2) tetramer and a gamma delta het erodimer. Class IV enzymes catabolize CO to CO2 and are alpha -subunit mono mers. Phylogenetic analyses were performed on all five subunits. ACS alpha sequences divided into 2 major groups, including Class I/II sequences and C lass III/IV-like sequences. Conserved residues that may function as ligands to the B- and C-clusters were identified. Other residues exclusively conse rved in Class I/II sequences may be ligands to additional metal centers in Class I and II enzymes. ACS beta sequences also separated into two groups, but they were less divergent than the alpha 's, and the separation was not as distinct. Class III-like beta sequences contained similar to 300 residue s at their N-termini absent in Class I/II sequences. Conserved residues ide ntified in beta sequences may function as ligands to active site residues u sed for acetyl-CoA synthesis. ACS gamma -sequences separated into 3 groups (Classes I, II, and III), while delta -sequences separated into 2 groups (C lass I/II and III). These groups are less divergent than those of alpha seq uences. ACS epsilon -sequence topology showed greater divergence and less c onsistency vis-a-vis the other subunits, possibly reflecting reduced evolut ionary constraints due to the absence of metal centers. The alpha subunit p hylogeny may best reflect the functional diversity of ACS enzymes. Scenario s of how ACS and ACS-containing organisms may have evolved are discussed.