Mini-Focus on metabolism

Chemical biology approaches have enhanced metabolism research through the detection of key metabolites and altering enzymatic reactions. This themed issue features a collection of articles that explore emerging research areas in the continual interplay between chemical biology and metabolism.

Cellular metabolism produces reactive metabolites as both main and side products, requiring recycling pathways to detoxify these products. A study uncovers a recycling pathway that protects vitamin B₁₂ from inactivating covalent modification.

This Review underscores the pivotal role of chemical biology in the discovery and characterization of fatty acid esters of hydroxy fatty acids, bioactive lipids linked to metabolic health and inflammation.

This Review highlights recent advances in the identification of small-molecule mediators of beta cell regeneration, discussing the diverse pathways and cellular processes altered by these compounds.

This Perspective highlights how metabolic states regulate diverse protein modifications that affect physiology. In addition, the roles of subcellular localization of metabolic enzymes and the importance of untargeted omics approaches are discussed.

CLYBL has a role beyond itaconate catabolism to degrade malyl-CoA, a noncanonical metabolite and methylmalonyl-CoA mutase inhibitor that depletes coenzyme B₁₂, implying that malyl-CoA contributes to the B₁₂ deficiency observed in individuals with CLYBL loss of function.

The MBD2c splicing variant of MBD2 that is essential for nuclear transcription translocates to the mitochondria to regulate mitochondrial DNA transcription and respiration and is linked to drug resistance in cancer cells.