Benzoyl Lysine (F5U6Z) Rabbit mAb #36723

Benzoyl lysine (Kbz) or lysine benzoylation is a reversible post-translational modification (PTM) that occurs on the ε-amine group of the lysine side chain. Kbz is derived from benzoyl-coenzyme A (benzoyl-CoA), an intermediate generated from the breakdown of sodium benzoate, a common food preservative, within mitochondria to form hippurate for excretion (1). In bacteria, benzoyl-CoA can be generated during the breakdown of diverse aromatic molecules beyond sodium benzoate to eventually form acetyl-CoA for energy (2). Enzymes that utilize benzoyl-CoA to form Kbz include KAT7 in humans and GcnE in Aspergillus flavus, and enzymes that remove Kbz include SIRT2 and SIRT3 in humans and Hst2 in Saccharomyces cerevisiae (3-6). Because the compounds that induce Kbz can have broad and conflicting effects, such as sodium benzoate impacting insulin secretion, and because many of the lysine benzoylation regulatory enzymes have shared roles in modulating other modifications such as acetylation, it can be challenging to discern Kbz-specific effects from Kbz-independent responses (1,7).

Kbz was initially discovered on histone proteins, yet Kbz-modified substrates extend into non-histone substrates, including alcohol dehydrogenase B (AdhB) in A. flavus and ATP-citrate lyase (ACLY) in humans (4,5,8). In the former case, AdhB competes with aflatoxin generation by converting the aflatoxin precursor acetaldehyde to ethanol. Mutation of a Kbz-modified site on AdhB to a non-lysine residue prevents Kbz formation and attenuates AdhB enzymatic activity, leading to increased aflatoxin production by the fungus (4). In the latter case, treating cells with sodium benzoate to elevate ACLY benzoylation or expressing an ACLY transgene encoded with a Kbz site using non-natural amino acids leads to reduced ACLY enzymatic activity (5).