## 1 Introduction  
The F\({}_{0}\)-F\({}_{1}\) ATPase synthase or H\({}^{+}\)-ATPase catalyzes the synthesis of ATP and inorganic phosphate and plays a crucial role in free energy transduction. The synthase is comprised of two complexes or subunits, F\({}_{0}\) and F\({}_{1}\). The inner membrane-embedded F\({}_{0}\) complex consists of the three catalytic subunits a, b, and c (1:2:10), and forms a proton channel through the membrane where proton translocation occurs. The catalytic and cytoplasmic F\({}_{1}\) complex consists of the \(\alpha\), \(\beta\), \(\gamma\), \(\delta\), and \(\varepsilon\) subunits (3:3:1:1:1). Central and peripheric stalks link F\({}_{0}\) and F\({}_{1}\) subunits together. The central stalk and a ring of the subunit c of the F\({}_{0}\) complex form a rotating structure whose rotation is driven by extracellular proton translocation across the F\({}_{0}\) complex, resulting in structural changes in the F\({}_{1}\) complex, leading in the synthesis of ATP from ADP and phosphate [1; 2; 3; 4; 5]. ATP plays a fundamental role in the cell's physiology by providing energy for essential processes such as active transport, central carbon metabolism, biosynthetic pathways, DNA, RNA, protein synthesis, signal transduction, motility, cellular division, and stress responses [6]. Under aerobic conditions, the H\({}^{+}\)-ATPase catalyzes the phosphorylation of ADP to ATP by using the proton motive force. Under anaerobic conditions, it energizes the inner membrane by proton extrusion dependent on ATP hydrolysis [2; 4; 7]. The ATP synthase operon consists of nine genes _atplBEFHAGDC_. The _atpBEF_ genes encode the F\({}_{0}\) subunits a, b, and c, respectively, whereas the _atpHAGDC_ encodes the F\({}_{1}\) subunits \(\delta\), \(\alpha\), \(\gamma\), \(\beta\), and \(\varepsilon\). The _atpl_ gene encodes for the accessory factor Atpl. The entire operon is transcribed as a polycistronic unit [2; 4]. The inactivation or overexpression of the partial or entire _atp_ operon results in perturbed ATP levels by modification of the [ATP]/[ADP] ratio, affecting the cell's metabolism and physiology significantly [8]. The expression of the F\({}_{1}\) subunit of the ATP synthase in the strain of _E. coli_ BOE270 by plasmid-cloning the genes _atpAGD_ (encoding the \(\alpha\), \(\gamma\), and \(\beta\) subunits) resulted in a cytoplasmic uncoupled activity, affecting the energy state of the cell, reflected by a lower [ATP]/[ADP] ratio and increased carbon flux through the glycolytic pathway (up to 70%) associated with a smaller decrease in the growth rate in the resultant derivative versus the parental strain. These results proposed that the control of the glycolysis resides outside the pathway, particularly on the enzymes hydrolyzing ATP [9]. Overexpression and inactivation, both in the F\({}_{1}\) subunit of the ATP synthase in _E. coli_ JM101, and the culture under aerobic conditions in an M9 mineral broth supplemented with glucose as the carbon source under aerobic conditions, resulted in derivative strains JMAGD\({}^{+}\) and JM_atp\({}^{-}\)_, respectively, with relevant metabolic changes. Both derivatives showed reduced energetic levels determined with the [ATP]/[ADP] ratio and cAMP level. Transcriptomic analysis of 105 genes, including the glycolytic and pentose phosphate pathways, TCA cycle, respiratory genes, acetate metabolism, and some regulators, showed a downregulation of the glycolytic, TCA cycle, and respiratory genes in both strains compared to the parental strain JM101 in response to a decrease in [ATP]/[ADP] ratio, and was associated with a reduction in the levels of cAMP. Still, in contrast, derivatives showed relevant increases in glucose and oxygen-specific consumption rates, a relevant trait for industrial production strains [6]. _Escherichia coli_ PB12 is a _AptsHlcrr_ (PTS\({}^{-}\) mutant) derivative strain of the parental strain JM101 [10].