Phosphoproteomic Reveals That Phosphoglycerate Kinase 2 Suppresses Hypoxanthine Accumulation in Broiler

Abstract

Recent studies have found that the amount and proportion of meat flavor–related metabolites differ among different parts of muscle, which is partly attributed to their diverse myofiber type composition. However, the genetic regulatory factors behind these meat flavor–related metabolites remain unclear. Here, to systematically identify the differences in meat flavor–related metabolite of different parts of muscle and explore their genetic causes, metabolome and transcriptome were performed by using breast and drumstick muscle in Guangming-2 chicken. Meat flavor–related metabolite-gene networks were constructed, and phosphoglycerate kinase 2 (PGK2), which was found to be negatively correlated with flavor–related metabolites such as hypoxanthine, lysine, and glycerophospholipids, was selected for further identification. AlkB homolog 5 (ALKBH5)–mediated m⁶A demethylation enhances RNA stability of PGK2. Lentivirus-mediated PGK2 overexpression and knockdown chicken models were constructed to study the function of PGK2. Gain- and loss-of-function analysis revealed that PGK2 promoted a switch from slow-twitch to fast-twitch fibers and suppressed the accumulation of hypoxanthine in vivo. Moreover, phosphoproteomic results demonstrated that PGK2 was involved in myofiber type transformation and meat flavor–related metabolite accumulation by modulating protein phosphorylation. Our findings deepen the understanding of the regulatory role of protein phosphorylation in meat flavor–related metabolite accumulation in broiler.