Recent advances and challenges in the biomanufacturing of L-homoserine as a versatile C4 platform chemical

Beyond its fundamental role as a central metabolic node in the L-aspartate pathway, L-homoserine is increasingly recognized as a flexible C4 building block applicable to the synthesis of various industrial bioproducts, including essential amino acids, bioplastics, and agrochemicals. Unlike traditional chemical synthesis typically involving harsh conditions, the bioproduction of L-homoserine offers a sustainable alternative characterized by mild reaction processes and environmental friendliness. Propelled by the rapid evolution of synthetic biology and metabolic engineering, efforts have not only increased the yield of L-homoserine cell factories but also facilitated the assembly and optimization of pathways for downstream derivatives. Despite substantial strides in the biomanufacturing of L-homoserine and associated value-added products, a systematic overview covering the integrated metabolic engineering tactics remains scarce. Here, we summarize the recent progress in constructing highly efficient L-homoserine cell factories, particularly using Escherichia coli and Corynebacterium glutamicum as chassis. Furthermore, the biosynthesis of high-value derivatives is highlighted to underscore the versatility of the L-homoserine platform. Overall, this review discusses current technical hurdles and emerging opportunities, offering a strategic roadmap for the development of robust microbial manufacturing platforms for these derivatives.