Directed Engineering of Escherichia coli Enables Efficient Biosynthesis of Cytidine 5'-Monophosphate (CMP)

Cytidine 5'-monophosphate (CMP) is widely used in the food and pharmaceutical industries as a key raw material for producing cytidine 5'-triphosphate, CDP-choline, and other drugs for brain injury repair. The current mainstream enzymatic catalysis process suffers from high substrate costs and limited reaction efficiency, while RNA hydrolysis yields complex mixtures and poses great challenges in separation and purification.

Recently, a research team published findings in ACS Omega, reporting the precise engineering of Escherichia coli via systematic metabolic engineering to successfully construct a high-efficiency CMP-producing strain. The study sequentially knocked out cytidine degradation genes, negative regulatory genes for pyrimidine biosynthesis, and genes related to CMP phosphatase and phosphorylation to block catabolic pathways. Meanwhile, rate-limiting enzymes and feedback inhibition-resistant genes were overexpressed to enhance synthetic flux.

After optimization, the CMP titer reached 1013.6 mg/L in shake-flask fermentation and a maximum of 15.3 g/L in fed-batch fermentation using a 50 L bioreactor. This technology represents the first realization of direct CMP production by E. coli fermentation, replacing costly enzymatic processes with low-cost fermentation. It exhibits remarkable industrialization potential and will drive cost reduction, efficiency improvement, and green upgrading of the nucleotide biomanufacturing industry.

FOR DETAIL: https://doi.org/10.1021/acsomega.3c07713

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