RECOMBINANT MICROORGANISM FOR PRODUCING CYTIDINE DIPHOSPHATE AND METHOD FOR PRODUCING CYTIDINE DIPHOSPHATE

摘要

The present invention provides a recombinant microorganism for producing citicoline and a method for producing citicoline by using the recombinant microorganism, wherein genes for degradation and utilization of citicoline, choline, and phosphocholine are knocked out, 5-hydroxy-CTP diphosphatase encoded by a CTP degradation gene is knocked out, and shunting of CTP, which is a CDP precursor, is blocked. Key enzymes in citicoline synthesis, including choline kinase that phosphorylates choline chloride into phosphocholine and phosphocholine cytidylyltransferase that catalyzes a reaction between phosphocholine and CDP to generate citicoline, are expressed appropriately. In addition, a pyrimidine nucleoside synthesis pathway is genetically engineered to remove feedback inhibition to the synthesis pathway. A yield of more than 20 g/L of citicoline can be obtained with recombinant strains in a 5-liter fermenter by means of a biological fermentation method, achieving industrial mass production with low citicoline production costs and less pollution; therefore, the method is a simple, environmentally friendly and has a relatively high promotion and application value.