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Lactylation (Kla) is a newly discovered protein post-translational modification driven by lactate. First identified by the team led by Prof. Yingming Zhao at the University of Chicago, lactylation has been shown to play key regulatory roles in tumor progression, immune inflammation, cardiovascular diseases, neurological disorders, and other pathological processes.
In 2024, in collaboration with PTM BIO, the research team successfully distinguished and characterized three lactylation-related isomeric modifications: L-lactylation (KL-la), D-lactylation (KD-la), and ce-lactylation (Kce).
As a newly reported lactylation-related modification, D-lactylation remains largely underexplored and offers significant research potential. Evidence suggests that abnormally elevated D-lactate levels are closely associated with multiple disease processes, including short bowel syndrome, acute neurological injury, liver dysfunction, and tumor initiation and progression. Therefore, D-lactate-mediated D-lactylation may play important roles in cancer, digestive system diseases, neurological disorders, and other disease areas.
As a leader in lactylation research, PTM BIO provides comprehensive L-lactylation and D-lactylation PTMomics analysis services. Powered by highly specific proprietary L-/D-lactylation antibodies and 10X quantitative proteomics technology, PTM BIO enables specific discrimination and identification of L-lactylation and D-lactylation, helping researchers uncover their distinct biological functions and molecular mechanisms. This provides more precise insights into medical questions related to cancer, immunity, and other disease areas.
Protein samples are first enzymatically digested into peptide mixtures. The modified peptides are then enriched using PTM BIO’s proprietary D-lactylation antibodies and optimized enrichment materials, enabling specific recognition and enrichment of D-lactylated peptides.
Finally, the enriched peptides are analyzed and quantified by liquid chromatography–tandem mass spectrometry (LC-MS/MS).
Figure:Specificity validation of pan-D-lactylation antibodies
D-lactylation is closely associated with D-lactate generated during metabolic processes. D-lactate is the major lactate enantiomer in prokaryotes, and its biosynthetic pathways include the methylglyoxal pathway, phosphoenolpyruvate pathway, and glycolytic pathway. In humans and eukaryotes, D-lactate can also be produced under certain conditions, including the glyoxalase pathway under pathological states and the glycolytic pathway.
As a newly reported lactylation-related modification, D-lactylation remains largely underexplored and offers significant research potential. Clinical studies have shown that abnormal accumulation of D-lactate is closely associated with multiple disease processes, including short bowel syndrome, acute neurological injury, liver dysfunction, and tumor initiation and progression.
Therefore, D-lactate–mediated D-lactylation may play important roles in cancer, digestive system diseases, neurological disorders, and other disease areas. Research on D-lactylation provides new perspectives for disease diagnosis and therapeutic development.
1.Di Zhang, et al., 2019, Metabolic regulation of gene expression by histone lactylation. Nature.
2.Di Zhang, et al., 2024, Lysine L-lactylation is the dominant lactylation isomer induced by glycolysis. Nat Chem Biol.
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