Acetyl-CoA carboxylase (ACC) in bacteria is composed of three components: biotin carboxylase， biotin carboxyl carrier protein， and carboxyltransferase. ACC catalyzes the first committed step in fatty acid synthesis: the carboxylation of acetyl-CoA to form malonyl-CoA via a two-step reaction. In the first half-reaction， biotin carboxylase catalyzes the ATP-dependent carboxylation of the vitamin biotin covalently linked to biotin carboxyl carrier protein. In the second half-reaction， the carboxyl group is transferred from biotin to acetyl-CoA by the enzyme carboxyltransferase， to form malonyl-CoA. In most Gram-negative and Gram-positive bacteria， the three components of ACC form a complex that require... More
Acetyl-CoA carboxylase (ACC) in bacteria is composed of three components: biotin carboxylase， biotin carboxyl carrier protein， and carboxyltransferase. ACC catalyzes the first committed step in fatty acid synthesis: the carboxylation of acetyl-CoA to form malonyl-CoA via a two-step reaction. In the first half-reaction， biotin carboxylase catalyzes the ATP-dependent carboxylation of the vitamin biotin covalently linked to biotin carboxyl carrier protein. In the second half-reaction， the carboxyl group is transferred from biotin to acetyl-CoA by the enzyme carboxyltransferase， to form malonyl-CoA. In most Gram-negative and Gram-positive bacteria， the three components of ACC form a complex that requires communication for catalysis， and is subject to feedback inhibition by acylated-acyl carrier proteins. This study investigated the mechanism of inhibition of palmitoyl-acyl carrier protein (PACP) on ACC. Unexpectedly， ACC was found to exhibit a significant hysteresis， meaning ACC was subject to inhibition by PACP in a time dependent manner. Pull-down assays demonstrated PACP does not prevent formation of the multiprotein complex， while steady-state kinetic analyses showed PACP inhibited ACC activity allosterically. Structure-activity analyses revealed that the pantothenic acid moiety of PACP is responsible for the inhibition of ACC. This study provides the first evidence of the hysteretic nature of ACC.
