Acetyl-CoA carboxylases (ACCs) are enzymes that catalyze the carboxylation of acetyl-CoA to produce malonyl-CoA. In mammals, ACC1 and ACC2 are two members of ACCs. ACC1 localizes in the cytosol and acts as the first and rate-limiting enzyme in the de novo fatty acid synthesis pathway. ACC2 localizes on the outer membrane of mitochondria and produces malonyl-CoA to regulate the activity of carnitine palmitoyltransferase 1 (CPT1) that involves in the β-oxidation of fatty acid. Fatty acid synthesis is central in a myriad of physiological and pathological conditions. ACC1 is the major member of ACCs in mammalian, mountains of documents record the roles of ACC1 in various diseases, such as cancer, diabetes, obesity. Besides, acetyl-CoA and malonyl-CoA are cofactors in protein acetylation and malonylation, respectively, so that the manipulation of acetyl-CoA and malonyl-CoA by ACC1 can also markedly influence the profile of protein post-translational modifications, resulting in alternated biological processes in mammalian cells. In the review, we summarize our understandings of ACCs, including their structural features, regulatory mechanisms, and roles in diseases. ACC1 has emerged as a promising target for diseases treatment, so that the specific inhibitors of ACC1 for diseases treatment are also discussed.

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N6-acetyl-L-lysine residue is abundant in dietary protein but less is known about its potential influences on the diet-consumers. We herein report that N6-acetyl-L-lysine residues in acetylated dietary protein directly contributes to the acetylome in animal. By feeding mice with deuterium-labelled N6-acetyl-L-lysine-proteins, we demonstrated that acetylated dietary protein is a direct source of N6-acetyl-L-lysine that can widely contribute the acetylome in organs of liver, brain, and lung in mice. In mammalian cells, N6-acetyl-L-lysine can be utilized by Lysyl-tRNA synthetase (KARS) to generate N6-acetyl-L-lysyl-tRNA, which introduces N6-acetyl-L-lysine into the growing nascent polypeptide and intra-translationally results in protein acetylation. Co-crystal structure of KARS in complex with N6-acetyl-L-lysyl-AMP and pyrophosphate, coupled with in vitro biochemical assays, further confirms a sequential mechanism that KARS produces N6-acetyl-L-lysyl-AMP and transfers the N6-acetyl-L-lysyl-moiety to lysine cognate tRNA to generate N6-acetyl-L-lysyl-tRNA. Together, the present study establishes a model that N6-acetyl-L-lysine bridges the influence of acetylated dietary protein to the acetylome in dietary protein-consumer. Importantly, an undocumented mechanism that intra-translationally deposit acetylation in nascent proteins has been proved. It might extend the repertoire of acetylome and improves our understandings in protein modification modes in cells.