Table 4.
Genes that have been engineered to improve central carbon metabolism in the HEK293 cell line.
| Gene | Function | Modification | Outcome | Recombinant Protein(s) | Reference |
|---|---|---|---|---|---|
| Pyruvate Carboxylase (PC) |
Catalyzes the conversion of pyruvate to oxaloacetate | Overexpression | Increased maximal cell density, viability, and glucose utilization. | Adenovirus | [77] |
| Decreased lactate and ammonia production. | Recombinant Interferon α2b | [78] | |||
| Improved glucose metabolism. | [79] | ||||
| Improved total volumetric recombinant protein production | [80] | ||||
| Pyruvate dehydrogenase kinase (PDK) | Inactivates the pyruvate dehydrogenase enzyme complex, increasing the conversion of pyruvate to lactate in the cytosol. | Knockdown | 30-fold increase in specific productivity of infectious viral particles and a 4-fold decrease in lactate production | Retroviral vectors | [81] |
| Hypoxia inducible factor 1 (HIF1A) | Activates an over-expression cascade of glycolytic enzymes and glycolysis-related genes, including pyruvate dehydrogenase kinase (PDK) and lactate dehydrogenase (LDH) | Knockdown |