The paper discovers that certain bacterial and human chaperone proteins (GroEL/Hsp60) can act like enzymes that break down or add fatty acid groups, especially using a molecule called palmitoyl‑CoA, but it does not study the peptide palmitoyl‑dipeptide‑6 or any health‑related effects.

Group I chaperonins are key proteins that control cell metabolism, stress adaptation and survival. They usually form a tetradecameric structure that assists, coupled to ATP hydrolysis, 10 % of all cellular protein folding. While working on TesA thioesterase activity, we serendipitously discovered that M. tuberculosis GroEL1 also had thioesterase activity. Using recombinant E. coli GroEL, human mitochondrial Hsp60 and GroEL1 and GroEL2 M. tuberculosis chaperonins, we found that these proteins all showed thioesterase activity. Focusing on M. tuberculosis chaperonins, we further identified that GroEL1 and GroEL2 also have esterase and auto-acyltransferase activities. The smaller oligomers of human Hsp60 and M. tuberculosis GroEL1 were able to use the long acyl carbon chain substrate palmitoyl-CoA, while tetradecameric E. coli GroEL and human Hsp60 were not. ATP, together with Mg, reduced GroEL1 dimerization, but, alone, also antagonized GroEL1 thioesterase activity. Alanine substitutions on six M. tuberculosis GroEL1 residues identified Asp86 and Thr89 in the ATP-binding pocket and an additional Ser393 as important residues for the thioesterase activity. Additionally, M. tuberculosis GroEL1 enhanced palmitoylation of the recombinant C-terminal half of the PpsE protein. As PpsE is required for phthiocerol dimycocerosate (PDIM) biosynthesis, this could explain, at least partly, the involvement of GroEL1 in M. tuberculosis PDIM biosynthesis and antibiotic resistance.