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).