Acetylation of Metabolic Enzymes Coordinates Carbon Source Utilization and Metabolic Flux

TLDR

Lysine acetylation regulates many eukaryotic cellular processes, but its function in prokaryotes is largely unknown, and it represents a conserved metabolic regulatory mechanism from bacteria to mammals. This modulation is mainly controlled by a pair of lysine acetyltransferase and deacetylase whose expressions are coordinated with growth status. We found that central metabolic enzymes in Salmonella are extensively and differentially acetylated in response to carbon source, regulating the activities of key enzymes that control glycolysis versus gluconeogenesis and the branching between the citrate cycle and glyoxylate bypass, and that reversible acetylation allows cells to sense energy status and flexibly alter reaction rates or directions.

Abstract

Lysine acetylation regulates many eukaryotic cellular processes, but its function in prokaryotes is largely unknown. We demonstrated that central metabolism enzymes in Salmonella were acetylated extensively and differentially in response to different carbon sources, concomitantly with changes in cell growth and metabolic flux. The relative activities of key enzymes controlling the direction of glycolysis versus gluconeogenesis and the branching between citrate cycle and glyoxylate bypass were all regulated by acetylation. This modulation is mainly controlled by a pair of lysine acetyltransferase and deacetylase, whose expressions are coordinated with growth status. Reversible acetylation of metabolic enzymes ensure that cells respond environmental changes via promptly sensing cellular energy status and flexibly altering reaction rates or directions. It represents a metabolic regulatory mechanism conserved from bacteria to mammals.