MOLECULAR EVOLUTION OF BIOTIN-DEPENDENT CARBOXYLASES

Amino-acid sequences of three functional units from various biotin-dependent carboxylases, biotin carboxylase, biotin-carboxyl-carrier protein and carboxyl transferase, were investigated by computer-assisted sequence comparison to obtain information about the structure, function, and molecular evolution of the enzymes. Biotin-dependent carboxylases, except transcarboxylase and oxaloacetate decarboxylase which lack biotin carboxylase, exert their catalytic activities through the three functional units. The three functional units correspond with functional domains or subunits of the enzymes, and the genetic information for the units is encoded in different ways from enzyme to enzyme. It is known that biotin carboxylase is homologous to carbamoyl-phosphate synthetase, and that the biotin-carboxyl-carrier protein is homologous to lipoic-acid-binding domain. The evolutionary relationships between the functional units and their homologues were described. A model for the evolutionary history of the enzymes was proposed by molecular phylogenetic analysis, which shows how a wide variety of domain and/or subunit structures for the enzymes may have been established. A repeated structure was found in biotin-carboxyl-carrier protein, and the secondary structure of the protein was predicted using the observed sequence similarity with a lipoic-acid-binding domain.