Microbial Ethylene Glycol Metabolism: Pathways, Metabolic Engineering, and PET Upcycling.

Ethylene glycol (EG) is an attractive non-sugar carbon source because it can be obtained from petrochemical routes, renewable production platforms, and the depolymerization of polyethylene terephthalate (PET), thereby linking plastic upcycling with sustainable biomanufacturing. In recent years, substantial progress has been made in elucidating EG catabolism, including the initial oxidation of EG, native glyoxylate assimilation pathways, synthetic route design, and chassis engineering. Nevertheless, efficient and robust EG bioconversion is still limited by unfavorable thermodynamics, low catalytic efficiency, intermediate toxicity, and pathway-host incompatibility. In this Review, we summarize recent advances in three interconnected areas: the oxidation of EG to glycolaldehyde and its downstream processing; glyoxylate-centered native assimilation networks and their integration with central carbon metabolism; and synthetic pathways designed to improve carbon conservation and redirect carbon flux toward acetyl-CoA, central metabolites, and target products. We compare the tartronate semialdehyde pathway with the β-hydroxyaspartate cycle, discuss key design principles for synthetic modules, and highlight recent progress in chassis engineering, regulatory rewiring, and the direct conversion of PET hydrolysates. We further emphasize the ongoing transition from single-substrate EG utilization to integrated PET upcycling, in which mixed-monomer co-utilization, impurity tolerance, and aldehyde detoxification have emerged as major engineering targets. Overall, EG is becoming a promising platform substrate for connecting plastic waste recycling with green biomanufacturing, although further advances in enzyme discovery, pathway optimization, and pathway-host matching are still required.