acetate

Acetic acid is a primary inhibitory by-product in Escherichia coli cultivation. Its accumulation adversely affects cellular growth, metabolism, and the synthesis of desired recombinant or metabolic products, primarily due to cytoplasmic acidification and disruption of energy metabolism [180]. Reducing acetate accumulation in Escherichia coli cultures limits carbon loss to overflow by-products and mitigates acetate-associated toxicity, thereby facilitating high–cell-density cultivation [133].
Several strategies can be applied to reduce acetate accumulation. The primary acetate-forming route converts acetyl-CoA to acetate via the acetyl-phosphate intermediate and is catalyzed by the phosphotransacetylase–acetate kinase system encoded by pta and ackA [131]. A secondary route generates acetate directly from pyruvate through pyruvate oxidase, encoded by poxB. Targeted disruption of these pathways diminishes acetate formation by limiting flux through its major biosynthetic routes. Additionally, acetate reassimilation can be enhanced by overexpressing acs, which converts acetate into acetyl‐CoA at the expense of ATP, thereby reincorporating residual acetate into central metabolism.