The present disclosure describes the engineering of microbial cells for fermentative production of histamine and provides novel engineered microbial cells and cultures, as well as related histamine production methods.

An adenosine-involved fully enzymatic synthesis method for NMN includes the steps under the same reaction system: (A) reacting, under the catalytic action of a yeast cell, adenosine, phosphate and sugar that is metabolizable by a yeast cell, so as to generate ATP; and (B) generating NMN by an enzymatic reaction including the step of under the action of NAMPT, reacting nicotinamide, PRPP and ATP to generate NMN, ADP and phosphate. In this way, a series of reactions such as the generation (regeneration) of ATP, the synthesis of NMN and the utilization of ATP are performed in one reaction system in a unified manner, and thus efficient synthesis of NMN can be implemented.

The present invention provides a method for preparing nicotinamide mononucleotide (NMN) by bioanalysis. The method includes a step of catalytically reacting a plurality of raw materials including nicotinamide, ATP, and ribose in the presence of nicotinamide phosphoribosyltransferase (Nampt), ribose phosphate pyrophosphokinase, and ribokinase, to prepare the NMN.

The present disclosure describes the engineering of microbial cells for fermentative production of histamine and provides novel engineered microbial cells and cultures, as well as related histamine production methods.

The present disclosure relates to a genetically engineered strain with high production of uridine and its construction method and application. The strain was constructed as follows: heterologously expressing pyrimidine nucleoside operon sequence pyrBCAKDFE (SEQ ID NO:1) on the genome of E coli prompted by strong promoter P.sub.trc to reconstruct the pathway of uridine synthesis; overexpressing the autologous prsA gene coding PRPP synthase by integration of another copy of prsA gene promoted by strong promoter P.sub.trc on the genome; deficiency of uridine kinase, uridine phosphorylase, ribonucleoside hydrolase, homoserine dehydrogenase I and ornithine carbamoyltransferase. When the bacteria was used for producing uridine, 40-67 g/L uridine could be obtained in a 5 L fermentor after fermentation for 40-70 h using the technical scheme provided by the disclosure with the maximum productivity of 0.15-0.25 g uridine/g glucose and 1.5 g/L/h respectively which is the highest level of fermentative producing uridine reported at present.

This disclosure provides mutant genes related to drug resistance and relapse of acute lymphoblastic leukaemia (ALL) and a use thereof, treatment or prevention of drug resistance and relapse of ALL and a use thereof, a use of compound Lometrexol and related inhibitors targeting GART and AITC in prevention and treatment of drug resistance and relapse of ALL, and a kit for evaluation of the risk of drug resistance and relapse of ALL. The mutation gene is a mutant gene of PRPS1. The drug acts on enzymes in purine synthesis pathway and reduces drug resistance and relapse by decreasing the concentration of hypoxanthine. The kit comprises reagents for lysis of sample cells and an instruction. The invention provides a powerful technical means and support for the prevention and treatment of drug resistance and relapse of ALL.

An object of the present invention is to provide a method for producing nicotinamide mononucleotide (NMN) with excellent production efficiency. The method for producing NMN according to the present invention (the first aspect) comprises the step of bringing a transformant with enhanced expression of enzymes nicotinamide phosphoribosyltransferase (Nampt), phosphoribosyl pyrophosphate synthetase (Prs) and polyphosphate kinase (Ppk), a cell-free protein synthesis reaction solution having the three enzymes expressed, or a treated product thereof into contact with a mixture containing ribose-5-phosphate (R5P), nicotinamide (NAM), ATP and polyphosphate.

The present invention relates to microbial production of nicotinamide mononucleotide (NMN), nicotinamide riboside (NR), and nicotinamide adenine dinucleotide (NAD) using a genetically modified bacterium.

The present disclosure describes the engineering of microbial cells for fermentative production of histamine and provides novel engineered microbial cells and cultures, as well as related histamine production methods.

The present disclosure relates to a genetically engineered strain with high production of uridine and its construction method and application. The strain was constructed as follows: heterologously expressing pyrimidine nucleoside operon sequence pyrBCAKDFE (SEQ ID NO:1) on the genome of E coli prompted by strong promoter P.sub.trc to reconstruct the pathway of uridine synthesis; overexpressing the autologous prsA gene coding PRPP synthase by integration of another copy of prsA gene promoted by strong promoter P.sub.trc on the genome; deficiency of uridine kinase, uridine phosphorylase, ribonucleoside hydrolase, homoserine dehydrogenase I and ornithine carbamoyltransferase. When the bacteria was used for producing uridine, 40-67 g/L uridine could be obtained in a 5 L fermentator after fermentation for 40-70 h using the technical scheme provided by the discloure with the maximum productivity of 0.15-0.25 g uridine/g glucose and 1.5 g/L/h respectively which is the highest level of fermentative producing uridine reported at present.