Abstract
The sustainable, bio-based production of industrially valuable chemicals and materials from renewable, non-edible biomass through biorefineries has emerged as a vital strategy for tackling urgent global challenges, including climate change, and for realizing the "net zero carbon" commitments recently pledged by nations worldwide. Metabolic engineering has played a central role in enabling the development of microbial strains capable of efficiently overproducing a diverse array of target compounds. Nevertheless, engineered microbial cell factories often face inherent trade-offs between product synthesis and cell growth, frequently resulting in diminished fitness or loss-of-function phenotypes. This review highlights recent advances in metabolic engineering strategies aims at reconciling this conflict, encompassing pathway optimization, dynamic regulation, orthogonal system design, microbial consortia engineering, fermentation process control, and integrative metabolic modeling. It also explores the remaining challenges and future directions for reprogramming microbial metabolism to harmonize growth with high-level production.