Related Experiment Video
Updated: Jun 24, 2026

05:58
Site-Specific Lysine Lactylation via Genetic Code Expansion in E. coli and Mammalian Cells
Published on: February 24, 2026
Lactate as a Chemical Modification on Proteins and Metabolites
Shuke Xiao1,2,3, Andrew L Markhard1,2, Jonathan Z Long4,1,3,2,5
1Department of Pathology, Stanford School of Medicine, Stanford, California, USA;
Annual Review of Biochemistry
|June 22, 2026
Summary
Lactate is more than a byproduct; it modifies proteins and amino acids. These modifications link glycolysis to cellular functions, impacting homeostasis.
Area of Science:
- Biochemistry
- Cellular Biology
- Metabolomics
Background:
- Lactate traditionally viewed as a glycolytic byproduct.
- Emerging roles: energy metabolite, redox shuttle, signaling molecule.
- Recent discovery: lactate as a chemical modification on proteins and metabolites.
Purpose of the Study:
- Review detection, regulation, and function of lactate modifications.
- Highlight lysine lactylation and N-lactoyl amino acids.
- Connect glycolytic flux to downstream effectors via lactate modifications.
Main Methods:
- Mass spectrometry for detecting lactate modifications.
- Review of existing literature on lactate modification.
- Analysis of cellular and organismal homeostasis.
Main Results:
- Identification of lysine lactylation on proteins.
- Characterization of N-lactoyl amino acids.
- Lactate modifications translate transient metabolic changes into durable signals.
Conclusions:
- Lactate modifications are crucial for cellular and organismal homeostasis.
- These modifications offer a new perspective on lactate biology.
- Further research into lactate's regulatory roles is warranted.
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Covalently Linked Protein Regulators
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These groups modify specific amino acids in a protein.
These groups modify specific amino acids in a protein.
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Proteins can undergo many types of post-translational modifications, often in response to changes in their environment. These modifications play an important role in the function and stability of these proteins. Covalently linked molecules include functional groups, such as methyl, acetyl, and phosphate groups, and also small proteins, such as ubiquitin. There are around 200 different types of covalent regulators that have been identified.
These groups modify specific amino acids in a protein.
These groups modify specific amino acids in a protein.
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Glycosylation, the most common post-translational modification for proteins, serves diverse functions. Adding sugars to proteins makes the proteins more resistant to proteolytic digestion. Glycosylated proteins can act as markers and receptors to promote cell-cell adhesion. Additionally, they have many essential quality control functions in the cell, such as correct protein folding and facilitating transport of misfolded proteins to the cytosol, which can be degraded.
Glycosylation occurs in...
Glycosylation occurs in...
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Broadly, these modifications can be categorized into four main categories — glycosylation, formation of disulfide bonds, assembly of protein subunits, and specific proteolytic cleavages like removal of signal sequences.
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Lactic acid, an important organic acid extensively applied in food, pharmaceutical, and biodegradable polymer industries, is primarily produced via microbial fermentation. This method is favored over chemical synthesis due to its environmental sustainability and capacity for enantiomerically pure product formation. Among various microbial processes, the fermentation of starch-based substrates stands out due to the abundance and renewability of raw materials like corn and potatoes.Hydrolysis of...
