Synthetic Biology Strategies for Harnessing Bacterial Glucose Oxidation Pathways

As the most important carbon source for bioproduction, glucose is transported and enters the central carbon metabolic pathway directly in most microorganisms. However, certain bacteria utilize membrane-bound dehydrogenases to oxidize glucose to gluconic acid (GA) in the periplasmic space. GA is subsequently converted either to 5-keto-d-gluconate by PQQ-dependent gluconate dehydrogenase (GADH) or to 2-keto-d-gluconate by FAD-dependent GADH, with the latter further oxidized to 2,5-diketo-d-gluconate. This review systematically examines the composition, distribution, physiological functions, and key enzymes of this oxidative pathway, alongside industrial applications of its metabolic products. Special emphasis is placed on metabolic engineering strategies─including bottleneck elimination, cofactor balancing, and chassis optimization─to overcome inherent regulatory constraints and enhance carbon flux toward target compounds. The potential of this pathway for the sustainable production of tartaric acid, 2,5-furandicarboxylic acid, vitamin C precursors, and phosphorus fertilizers is comprehensively assessed.