Here, our data suggested a possible role of acetyl-CoA synthetase as a key enzyme that allows the binding of lactate to the same binding site as acetate. Interestingly, active site binding amino acid residues such as TRP413, TRP414, GLN415, ARG515, ASN521 are earlier reported in case of acetyl-CoA synthetase as in case of lactate vs. acetate . These findings hinted at the potential uses of acetyl-CoA synthetase by cancer cells to generate lactyl-CoA for the proposed lactylation process because of metabolic reprogramming. Then non-cancer cells including microbiotas with suitable enzymes may convert lactate to lactyl-CoA and then lactyl-CoA is released into the tumor microenvironment . The role of acetyl-CoA synthetase is depicted in the activation of macrophages mediated by pro-inflammatory bacteria (28-30).