Improving succinate production by engineering oxygen-dependent dynamic pathway regulation in Escherichia coli

Recent Progress in Metabolic Engineering of Escherichia coli for the Production of Various C4 and C5-Dicarboxylic Acids

“…Any imbalance can result in a metabolic burden that can impede effective production . Addressing these challenges required dynamic regulation that replicates the metabolic control systems of various organisms, allowing cells to alter metabolic flux by detecting external stress or intracellular conditions, thereby mitigating the metabolic burden and facilitating efficient chemical production. ,− …”

“…102 A succinate production strain with osmo-tolerant mutations was engineered to utilize an oxygen-sensitive bifunctional switch (OBS) to maintain efficient production under osmotic stress, potentially leading to decrease of production performance. 100 The OBS allowed the global regulator FNR to augment the expression of pck from Actinobacillus succinogenes under anaerobic conditions while reducing endogenous pykAF. This dynamic regulation increased succinate production, achieving a final titer of 119 g/L with a yield of 1.06 g/g glucose in 72 h using a 30 L fermenter.…”

“…This dynamic regulation increased succinate production, achieving a final titer of 119 g/L with a yield of 1.06 g/g glucose in 72 h using a 30 L fermenter. 100 To improve malate production, a temperature-dependent dynamic control approach was implemented using temperature-sensitive malate dehydrogenase (Mdh) from Rhodomicrobium vannielii, preventing malate degradation. 103 The modified strain underwent cultivation in three stages.…”

“…The OBS allowed the global regulator FNR to augment the expression of pck from Actinobacillus succinogenes under anaerobic conditions while reducing endogenous pykAF . This dynamic regulation increased succinate production, achieving a final titer of 119 g/L with a yield of 1.06 g/g glucose in 72 h using a 30 L fermenter . To improve malate production, a temperature-dependent dynamic control approach was implemented using temperature-sensitive malate dehydrogenase (Mdh) from Rhodomicrobium vannielii , preventing malate degradation .…”