Cyclic AMP-dependent Protein Lysine Acylation in Mycobacteria Regulates Fatty Acid and Propionate Metabolism

Abstract

Background: KATmt is the first identified cAMP-regulated protein lysine acetylase in mycobacteria. Results: KATmt acylates fatty acyl CoA ligases in vivo in a cAMP-dependent manner, thus regulating their activity. Conclusion: Mycobacteria utilize KATmt to regulate the metabolic pool of acetyl and propionyl CoA. Significance: We provide novel paradigms for linking cAMP signaling and fatty acid metabolism in mycobacteria.

Allosteric Regulation of a Protein Acetyltransferase in Micromonospora aurantiaca by the Amino Acids Cysteine and Arginine

“…AcetylCoA and NAD are key indicators of cellular energy status and demonstrate that protein lysine acetylation serves as a link that connects cellular energy levels with protein acetylation/ deacetylation activity. In mycobacteria, cAMP directly activates MsKat and MtKat by binding of cAMP to the cyclic nucleotide-binding domain of two protein acetyltransferases, indicating that the levels of protein acetylation can also be modulated by response to intracellular cAMP levels (27). This study demonstrated that ACT domains are linked to GNAT acetyltransferases, which confirms amino acid-induced allosteric regulation of these enzymes.…”

Loving the poison: the methylcitrate cycle and bacterial pathogenesis

“…Propionylation of acyl-CoA synthase in M. bovis BCG leads to diminished synthesis of propionyl-CoA from propionate [33]. Indeed, a considerable number of propionylated proteins have been identified in this species, possibly defining another 'sink' for excess propionyl-CoA.…”

“…For example, propionate metabolism in Mycobacterium smegmatis is regulated by lysine acetylation [32] and a cAMP-dependent protein lysine acetyltransferase in Mycobacterium bovis BCG (KATmt) has been shown to be necessary for growth on propionate as a sole carbon source [33].…”

Acylation of Biomolecules in Prokaryotes: a Widespread Strategy for the Control of Biological Function and Metabolic Stress

“…An independent study identified eight additional acyl-CoA synthetases as the substrates of MsPatA (192). The single protein deacetylase in M. tuberculosis, an NAD ϩ -dependent sirtuin homologue (MRA_1161, from H37Ra), deacetylated MtAcs and all eight acyl-CoA synthetases in vitro (178,192), suggesting that that this likely constitutes a regulatory system comparable to the RLA systems found in S. enterica and R. palustris (196).…”

“…In these organisms, the GNAT domain is attached to a cyclic AMP (cAMP) binding domain (type III) (178,191). cAMP allosterically activates MtPatA and MsPatA, enhancing their activity Ͼ2-fold (178,(191)(192)(193)(194).…”