Fig. 1
From: Emerging roles of non-histone protein crotonylation in biomedicine
The metabolic pathways and enzymes and modulators for lysine crotonylation (Kcr). Colon microbiota is a source of short chain fatty acids (SCFAs) which may be metabolized to acetyl/crotonyl/propionyl/butyryl-CoA in host cells. These CoAs are precursors used by enzymes to promote lysine acetylation (Kac), crotonylation (Kcr), propionylation, and butyrylation of histone and non-histone proteins. Currently characterized crotonyltransferases (KCTs) (writer) include CBP/P300, MYST, and GNAT family, and histone decrotonylases (KDCRs) (eraser) include HDAC I and HDAC III. When substrates are histone proteins, Kcr readers, including bromodomains, YEATS, and DPF domain, recognize the Kcr. Chromodomain Y-like (CDYL), acting as a crotonyl-CoA hydratase which converts crotonyl-CoA to β-hydroxybutyryl-CoA, negatively regulates crotonylation. ACCS2, acyl-CoA synthetase short chain family member 2. Inhibitors of P300/CBP include C646 and SGC-CBP30. Inhibitors of HDACs include trichostatin A (TSA), nicotinamide (NAM), suberoylanilide hydroxamic acid (SAHA), and LBH589