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.

The present invention relates to an attenuated Salmonella gallinarum strain and use thereof. Particularly, the present invention relates to: a novel attenuated Salmonella strain in which all of a gene encoding guanosine tetraphosphate (ppGpp) synthetase, a gene that induces the function of a type III secretion system (T3SS)(ssrAB), and a Gifsy 2prophage gene are deleted; and a composition for treating or diagnosing tumors by using same.

The present invention relates to recombinant Escherichia coli (E. coli) host cells comprising, in relation to wild-type cells, at least one mutation selected from the group consisting of deletion of the gene relA (relA); amino acid substitutions R290E and K292D in the protein guanosine-3,5-bis pyrophosphate 3-pyrophosphohydrolase (bifunctional (p)ppGpp synthetase II; SpoT) (spo T[R290E;K292D]); and amino acid substitution G267C in the protein pyruvate dehydrogenase subunit E1 (AceE) (aceE[G267C]). Said recombinant host cells are characterized by increased sugar uptake rates that lead to increased productivity when using said cells for the production of biosynthetic products. The present invention further relates to respective methods for the biosynthetic production of a product of interest using said host cells.

Enzyme-based systems and methods for synthesizing the NAD precursors NMN and NaMN are disclosed. Such methods and systems utilize a mutated form of phosphoribosylpyrophosphate synthetase (PRS) that is superactive and/or other enzyme or enzyme combinations that are immobilized onto a solid surface. The methods and systems substantially increase the efficiency and yield of NAD precursor synthesis.

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, wherein the instruction comprises: (i) collection and lysis of the sample cells; (b) determination of the contents of hypoxanthine, IMP, AICAR and Inosine; (c) evaluation of the risk of the drug resistance and relapse of ALL. The invention provides a powerful technical means and support for the prevention and treatment of drug resistance and relapse of ALL.

The invention provides non-naturally occurring microbial organisms containing an alkene pathway having at least one exogenous nucleic acid encoding an alkene pathway enzyme expressed in a sufficient amount to convert an alcohol to an alkene. The invention additionally provides methods of using such microbial organisms to produce an alkene, by culturing a non-naturally occurring microbial organism containing an alkene pathway as described herein under conditions and for a sufficient period of time to produce an alkene.

Provided is a recombinant microorganism for producing carnosine, histidine and beta-alanine and a method for producing carnosine, histidine and beta-alanine by using same and, more particularly, to: a recombinant microorganism for high production of carnosine, histidine and beta-alanine produced through the redesign of metabolic pathways; a method for producing same; and a method for producing carnosine, histidine and beta-alanine by using same. According to the present invention, in a microorganism capable of producing histidine and beta-alanine, by enhancing the pentose phosphate pathways through the replacement of a pentose phosphate pathway-related operon gene with a highly expressing synthetic promoter and the replacement of a pgi gene with an initiation codon, and inducing enhancement of the production of histidine and beta-alanine through the overexpression of genes on histidine and beta-alanine metabolic pathways, respectively, it is possible to develop a recombinant microorganism for high production of histidine and beta-alanine.

In this invention, cell lines are created for enzyme inhibitory testing of inhibitors against Plasmodium falciparum DHFR-TS and HPPK-DHPS. Provided the complementing DHFR-TS and HPPK-DHPS have sufficient activities to support growth of the surrogates in un-supplemented medium, the same surrogates could be used for screening inhibitors of targets against other parasite and pathogen species e.g. Plasmodium vivax, Trypanosoma brucei, Trypanosoma cruzi, Toxoplasma gondii or Mycobacterium tuberculosis. The cell lines in this invention are Escherichia coli strain whose thyA, folA, folK, and folP genes were disrupted using genetic knockout coupled with elimination of antibiotic resistance markers. The thyA KO, folP KO, folK KO, thyAfolA KO, folKfolP KO, thyAfolAfolP KO, thyAfolAfolK KO and thyAfolAfolKfolP KO E. coli cell lines are easy and convenient for testing single and combination drugs as plasmids bearing complementing parasite genes can be introduced simply by transformation using standard antibiotic selection.

Enzyme-based systems and methods for synthesizing the NAD precursors NMN and NaMN are disclosed. Such methods and systems utilize a mutated form of phosphoribosylpyrophosphate synthetase (PRS) that is superactive and/or other enzyme or enzyme combinations that are immobilized onto a solid surface. The methods and systems substantially increase the efficiency and yield of NAD precursor synthesis.

The invention provides non-naturally occurring microbial organisms containing an alkene pathway having at least one exogenous nucleic acid encoding an alkene pathway enzyme expressed in a sufficient amount to convert an alcohol to an alkene. The invention additionally provides methods of using such microbial organisms to produce an alkene, by culturing a non-naturally occurring microbial organism containing an alkene pathway as described herein under conditions and for a sufficient period of time to produce an alkene.