L-homoserine is an important non-proteinogenic amino acid with wide-ranging applications in the feed, pharmaceutical, and chemical industries.Currently, the synthesis of L-homoserine mainly relies on two technical routes:chemical synthesis and microbial fermentation.Among them, microbial fermentation has attracted considerable attention due to its environmental friendliness and cost-effectiveness, and is regarded as a promising approach for the green manufacturing of L-homoserine.Corynebacterium glutamicum, a food-grade industrial microorganism, has emerged as a promising host for L-homoserine production.However, current metabolic engineering efforts targeting C.glutamicum remain limited, and the achieved titers and yields of L-homoserine are still insufficient to meet the demands of industrial-scale applications.In this study, C.glutamicum was employed as the chassis strain for systematic metabolic engineering to construct a robust L-homoserine-producing cell factory.By eliminating degradation pathways and reconstructing the dual biosynthetic routes involving AspC and AspA, a basal chassis strain with L-homoserine biosynthetic capacity was first established.Subsequently, further improvements were achieved through enhancing precursor supply, fine-tuning the metabolic fluxes of the dual pathways, and optimizing NADPH regeneration.The final engineered strain, HOM21, achieved a titer of 95.8 g/L in a 5-liter bioreactor, with a production rate of 1.6 g/(L·h) and a glucose conversion yield of 0.45 g/g, representing the highest level of L-homoserine production reported for C.glutamicum to date.This study provides a comprehensive metabolic engineering strategy for the efficient biosynthesis of L-homoserine in C.glutamicum, elucidates key rate-limiting steps and their regulatory optimization, and offers theoretical and practical guidance for the industrial-scale green production of L-homoserine.
PAN Yue
,
ZHANG Xinyu
,
LIU Qingdai
,
LIU Jun
,
WEI Liang
. Balanced regulation of dual pathways for efficient L-homoserine production in Corynebacterium glutamicum[J]. Food and Fermentation Industries, 2026
, 52(5)
: 35
-43
.
DOI: 10.13995/j.cnki.11-1802/ts.042849
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