Construction of an Efficient O-Succinyl-L-homoserine Producing Cell Factory and Its Application for Coupling Production of L-Methionine and Succinic Acid

O-Succinyl-L-homoserine (OSH) is an important C4 platform compound with broad applications. Its green and efficient production is receiving increasing attention. Herein, the OSH producing chassic cell was constructed by deleting the transcriptional negative regulation factor, blocking the OSH consumption pathway, and inhibiting the competitive bypass pathways. The precursor synthesis pathways of aspartic acid and homoserine were further strengthened, and the pentose phosphate pathway and glycolysis pathway were modified to enhance the NADPH supply. Adaptive evolution was applied to improve the tolerance of the cell factory to the fermentation environment. With Raman online analysis, the metabolic process model was built to guide fermentation regulation. The final titer of OSH reached 121.7 g/L with conversion of 63% in a 50 L fermenter. Based on this, a coupling production route for L-methionine and succinic acid from OSH was established with good atomic economy and environmental friendliness.