Malonyl-Proteome Profiles of Staphylococcus Aureus Reveal Lysine Malonylation Modification in Enzymes Involved in Energy Metabolism
Background
Protein lysine malonylation, a novel post-translational modification (PTM), has been recently linked with energy metabolism in bacteria. Staphylococcus aureus is the third most important foodborne pathogen worldwide. Nonetheless, substrates and biological roles of malonylation are still poorly understood in this pathogen.
Results
Using anti-malonyl-lysine antibody enrichment and high-resolution LC-MS/MS analysis, 440 lysine-malonylated sites were identified in 281 proteins of S. aureus strain. The frequency of valine in position -1 and alanine at +2 and +4 position was high. KEGG pathway analysis showed that six categories were highly enriched: ribosome, glycolysis/gluconeogenesis, pentose phosphate pathway (PPP), tricarboxylic acid cycle (TCA), valine, leucine, isoleucine degradation, and aminoacyl-tRNA biosynthesis. In total, 31 malonylated sites in S. aureus shared homology with lysine-malonylated sites previously identified in E. coli, indicating malonylated proteins are highly conserved among bacteria. Key rate-limiting enzymes in central carbon metabolic pathways were also found to be malonylated in S. aureus, namely pyruvate kinase (PYK), 6-phosphofructokinase, phosphoglycerate kinase, dihydrolipoyl dehydrogenase, and F1F0-ATP synthase. Notably, malonylation sites were found at or near protein active sites, including KH domain, thioredoxin, alanine dehydrogenase (ALD), dihydrolipoyl dehydrogenase (LpdA), pyruvate oxidase CidC and catabolite control protein A (CcpA), thus suggesting that lysine malonylation may affect the activity of such enzymes.
Conclusions
Data presented herein expand the current knowledge on lysine malonylation in prokaryotes and indicate potential roles of protein malonylation in bacterial physiology and metabolism.
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Posted 06 Dec, 2020
Received 06 Dec, 2020
On 06 Dec, 2020
Received 26 Nov, 2020
On 23 Nov, 2020
Invitations sent on 22 Nov, 2020
On 22 Nov, 2020
On 21 Nov, 2020
On 21 Nov, 2020
On 21 Nov, 2020
Posted 23 Oct, 2020
On 12 Jan, 2021
Received 10 Nov, 2020
On 10 Nov, 2020
On 04 Nov, 2020
Received 02 Nov, 2020
On 29 Oct, 2020
Received 29 Oct, 2020
On 27 Oct, 2020
Invitations sent on 26 Oct, 2020
On 26 Oct, 2020
On 19 Oct, 2020
On 19 Oct, 2020
On 18 Oct, 2020
On 18 Oct, 2020
Malonyl-Proteome Profiles of Staphylococcus Aureus Reveal Lysine Malonylation Modification in Enzymes Involved in Energy Metabolism
Posted 06 Dec, 2020
Received 06 Dec, 2020
On 06 Dec, 2020
Received 26 Nov, 2020
On 23 Nov, 2020
Invitations sent on 22 Nov, 2020
On 22 Nov, 2020
On 21 Nov, 2020
On 21 Nov, 2020
On 21 Nov, 2020
Posted 23 Oct, 2020
On 12 Jan, 2021
Received 10 Nov, 2020
On 10 Nov, 2020
On 04 Nov, 2020
Received 02 Nov, 2020
On 29 Oct, 2020
Received 29 Oct, 2020
On 27 Oct, 2020
Invitations sent on 26 Oct, 2020
On 26 Oct, 2020
On 19 Oct, 2020
On 19 Oct, 2020
On 18 Oct, 2020
On 18 Oct, 2020
Background
Protein lysine malonylation, a novel post-translational modification (PTM), has been recently linked with energy metabolism in bacteria. Staphylococcus aureus is the third most important foodborne pathogen worldwide. Nonetheless, substrates and biological roles of malonylation are still poorly understood in this pathogen.
Results
Using anti-malonyl-lysine antibody enrichment and high-resolution LC-MS/MS analysis, 440 lysine-malonylated sites were identified in 281 proteins of S. aureus strain. The frequency of valine in position -1 and alanine at +2 and +4 position was high. KEGG pathway analysis showed that six categories were highly enriched: ribosome, glycolysis/gluconeogenesis, pentose phosphate pathway (PPP), tricarboxylic acid cycle (TCA), valine, leucine, isoleucine degradation, and aminoacyl-tRNA biosynthesis. In total, 31 malonylated sites in S. aureus shared homology with lysine-malonylated sites previously identified in E. coli, indicating malonylated proteins are highly conserved among bacteria. Key rate-limiting enzymes in central carbon metabolic pathways were also found to be malonylated in S. aureus, namely pyruvate kinase (PYK), 6-phosphofructokinase, phosphoglycerate kinase, dihydrolipoyl dehydrogenase, and F1F0-ATP synthase. Notably, malonylation sites were found at or near protein active sites, including KH domain, thioredoxin, alanine dehydrogenase (ALD), dihydrolipoyl dehydrogenase (LpdA), pyruvate oxidase CidC and catabolite control protein A (CcpA), thus suggesting that lysine malonylation may affect the activity of such enzymes.
Conclusions
Data presented herein expand the current knowledge on lysine malonylation in prokaryotes and indicate potential roles of protein malonylation in bacterial physiology and metabolism.
Figure 1
Figure 2
Figure 3
Figure 4
Figure 5
Figure 6
Figure 7