Lysine acetylation decreases enzyme activity and protein level of lactate dehydrogenase.

Lactate is an important bulk chemical with widespread applications and a major byproduct of other chemicals bioprocess in microbial fermentation. Lactate dehydrogenase A (LdhA) catalyzes the synthesis of lactate from pyruvate. Lysine acetylation is an evolutionarily conserved post-translational modification; however, the mechanisms underlying the regulation of LdhA function by lysine acetylation in remain poorly understood. Herein, we demonstrate acetylation of LdhA occurs via enzymatic and non-enzymatic mechanisms. Further, we show carbon source type and concentration affect the lysine acetylation status of LdhA via a non-enzymatic mechanism. Lysine acetylation significantly inhibits the enzymatic activity and protein level of LdhA. The results of the present study demonstrate lysine acetylation of LdhA is irreversible. Understanding of the effects of lysine acetylation on LdhA function may provide a new perspective for regulating lactate production in microbial synthesis.