Engineering the glycolytic pathway: A potential approach for improvement of biocatalyst performance

Abstract

The glycolytic pathway is a main driving force in the fermentation process as it produces energy, cell component precursors, and fermentation products. Given its importance, the glycolytic pathway can be considered as an attractive target for the metabolic engineering of industrial microorganisms. However, many attempts to enhance glycolytic flux, by overexpressing homologous or heterologous genes encoding glycolytic enzymes, have been unsuccessful. In contrast, significant enhancement in glycolytic flux has been observed in studies with bacteria, specifically, Corynebacterium glutamicum. Although there has been a recent increase in the number of successful applications of this technology, little is known about the mechanisms leading to the enhancement of glycolytic flux. To explore the rational applications of glycolytic pathway engineering in biocatalyst development, this review summarizes recent successful studies as well as past attempts.

Keywords: biochemicals; biofuels; corynebacterium glutamicum; fermentation; glycolytic pathway; metabolic engineering.

Figure 1.

Glycolysis via the EMP and ED pathways. Names of enzymes are underlined. Abbreviations: 6PGD, gluconate 6-phosphate dehydratase; 6PGL, 6-phosphogluconolactonase; ENO, enolase; FBA, fructose 1,6-bisphosphate aldolase; G6PDH, glucose 6-phosphate dehydrogenase; GAPDH, glyceraldehyde 3-phosphate dehydrogenase; GLK, glucokinase; GPI, glucose 6-phosphate isomerase; KDPGA, 2-keto-3-deoxy-6-phosphogluconate aldolase; PFK, 6-phosphofructokinase; PGK, phosphoglycerate kinase; PGM, phosphoglycerate mutase; PTS, phosphoenolpyruvate:carbohydrate phosphotransferase system; PYK, pyruvate kinase; TPI, triosephosphate isomerase; DHAP, dihydroxyacetone phosphate; GAP, glyceraldehyde 3-phosphate; KDPG, 2-keto-3-deoxy-6-phosphogluconate.