Insights into the methodology of acetyl-CoA carboxylase inhibition

Acetyl-CoA carboxylase catalyzes the first committed and regulated step in fatty acid synthesis in all animals, plants and bacteria. In most Gram-positive and Gram-negative bacteria, the enzyme is composed of three proteins: biotin carboxylase, biotin carboxyl carrier protein and carboxyltransferase. The reaction consists of two half-reactions. The first half reaction is catalyzed by biotin carboxylase and involves the carboxylation of the vitamin biotin which is covalently attached to the biotin carboxyl carrier protein. The second half reaction catalyzed by carboxyltransferase involves the transfer of the carboxyl group from biotin to acetyl-CoA to form malonyl-CoA. This chapter will describe the inhibitors of both the biotin carboxylase and carboxyltransferase components of bacterial acetyl-CoA carboxylase. Inhibitors that were used in the elucidation of the structure and mechanism of the enzyme will be discussed first. The second half will focus on inhibitors that also possess antibacterial activity.