4.1.2.1 Regulation of acetate metabolism by protein acetylation
Acetate overflow is a phenomenon that occurs when E. coli grows aerobically on glucose as the only carbon source. Under these conditions, there is an imbalance between glucose absorption and its conversion into biomass and products, causing the excretion of significant amounts of acetate (Bernal et al., 2016). The produced acetate can be used after depletion of the primary carbon source by the acetyl-CoA synthetase (Acs), which activates acetate to acetyl-coenzyme A (Ac-CoA), which is mainly metabolized by the glyoxylate shunt and the TCA cycle (Castaño-Cerezo et al., 2015). Acs is tightly controlled at the transcriptional level, and its activity, as mentioned above, is posttranslationally regulated by protein acetyltransferase.
The physiological role of Acs in acetate metabolism has been studied inE. coli strains with different genetic backgrounds. In knockout mutant ∆cobB and ∆acs, a similar phenotype was observed. Both strains produce acetate in glucose carbon-limited cultures, where yield is limited by its inability to scavenge overflown acetate (Castaño-Cerezo et al., 2014). The ∆coB mutant shows a reduced growth rate dependent on acetate concentration, as well as a reduction in the enzymatic activity of Acs in acetate cultures (Castaño-Cerezo et al., 2011; Castaño-Cerezo et al., 2014; Peebo et al., 2014). The growth at high and low acetate concentrations is restored in the double cobB-yfiQ- mutant (Castaño-Cerezo et al., 2011). The results demonstrate that protein acetylation plays an essential role in regulating overflow metabolism by modulating the activity of Acs. The inactivation of the enzyme limits acetyl-CoA synthesis, leading to acetate accumulation and growth inhibition.
Furthermore, acetylation of Acs may be involved in the control of the co-utilization of fermentable substrates. A random mutation in Leu-641 makes acetyl-CoA synthetase insensitive to acetylation even in high glucose concentrations (Starai & Escalante, 2005). The overexpression in E. coli W of this protein allows the efficient co-utilization of glucose and acetate. In a batch process containing glucose and high acetate concentrations, an increase of 2.7-fold in acetate up taken compared to a control strain was observed (Novak et al., 2018).