37 results about "Serine hydroxymethyltransferase" patented technology

In some aspects, methods of inhibiting survival or proliferation of a tumor cell are provided, the methods comprising inhibiting the glycine cleavage system (GCS) of the tumor cell. In some aspects, methods of treating a subject in need of treatment for a tumor, the method comprising inhibiting the GCS in the tumor. In some embodiments, the methods comprise contacting a tumor cell or tumor with a GCS inhibitor. In some embodiments, the tumor cell or tumor has elevated expression of serine hydroxymethyltransferase 2 (SH1VIT2). In some aspects, methods of identifying a tumor cell or tumor that is sensitive to inhibiting the GCS are provided, the methods comprising determining whether the tumor cell or tumor overexpresses SHMT2. In some aspects, methods of identifying a candidate anti-cancer agent are provided, the methods comprising identifying or modifying a GCS inhibitor.

The invention discloses a synthetic method of L-serine, which comprises the following steps: A) transforming the concentration of a substrate: adding the substrate, namely glycine and serine hydroxymethyltransferase accounting for 3%-8% by weight into a biological reactor; feeding 37% of formaldehyde water solution when the temperature is 40-50 DEG C and getting L-serine transformation liquid by transformation; B) purifying through an ultrafiltration membrane: purifying the L-serine transformation liquid in the A) step through the ultrafiltration membrane under the conditions that the temperature is 25-35 DEG C, the pressure at an inlet is 0.4-0.8MPa and the pressure at an outlet is 0.1-0.3MPa; C) performing adsorption and elution through ion-exchange resin: regulating the pH value of penetrating fluid in the B) step to 4.5-5.5, then exchanging the L-serine transformation liquid onto resin through the ion-exchange resin and further eluting with 0.8-1.5mol/L of hydrochloric acid; D) concentrating through a nanofiltration membrane: concentrating L-serine eluent in the step C) through the nanofiltration membrane under the conditions that the temperature is 25-35 DEG C, the pressure at the inlet is 0.4-0.8MPa and the pressure at the outlet is 0.1-0.3MPa; and getting an L-serine finished product after concentration. The synthetic method of the L-serine is simple in operation, short in production period, low in cost, high in yield and low in environmental protection pressure, and suitable for large-scale industrialized production.

The present invention discloses one kind of recombinant methylotrophic bacillus and its application. The recombinant methylotrophic bacillus MB202 is obtained through inserting glyA into the polyclonal site of pLAFR3 to obtain recombinant vector pLAFRg, and the subsequent three parent crossbreeding to introduce pLAFRg into methylotrophic bacillus MB200 to obtain the recombinant methylotrophic bacillus MB202. Through shaking table culture of MB202 at 32 deg.c in 50mM Tris-HCl culture medium with glycine in 10 mg/ml, methanol in 50 mg/ml, and biomass of 10<8>-10<9> CFU/ml, in pH 8.5 for 48 hr, L-serine yield may reach 11.5mg/ml; and through fermentation culture of MB202 at 32 deg.c for 12 hr, the activity of serine hydroxymethlase may reach 115 U. The recombinant methylotrophic bacillus MB202 has broad application foreground in producing L-serine and treating methanol waste water.

The present invention provides a component having effects in vivo of improving or optimizing the intestinal environment, suppressing intestinal putrefaction, or suppressing alternation of intestinal bacterial growth and/or pathological changes of intestinal bacterial growth in gut microbiota. The invention also provides an active ingredient suitably used for treating intestinal diseases. The invention provides a monoclonal IgA antibody that binds to amino acids 11 to 333 of serine hydroxymethyltransferase.

The present invention relates to a method for the treatment of cancer or an autoimmune disorder, comprising the administration of a serine hydroxymethyltransferase (SHMT) inhibitor, and in particular the administration of pyrazolopyran compounds of Formula (VI) as presently described, wherein the compounds are capable of inhibiting a mammalian SHMT, such as human SHMT1 and/or SHMT2. The treatment method further comprises the optional administration of an additional agent as a rescue therapy to reduce toxicity, wherein said agent may be chosen from formate, a formate salt, folinic acid, formate ester, or leucovorin.

The invention provides a biological synthesis method for increasing the accumulation of L-5-methyltetrahydrofolate, an L-5-methyltetrahydrofolate synthetase system co-expressed recombinant plasmid and a construction method and application thereof. The L-5-methyltetrahydrofolate synthetase system co-expressed recombinant plasmid comprises serine hydroxymethyltransferase (SHMT) gene GlyA and methylenetetrahydrofolate reductase (MTHFR) gene MetF sequences. The biological synthesis method for increasing the accumulation of the L-5-methyltetrahydrofolate comprises the following steps: converting for accumulating an original strain of the L-5-methyltetrahydrofolate to obtain a recombinant strain by virtue of the L-5-methyltetrahydrofolate synthetase system co-expressed recombinant plasmid, and fermenting the recombinant strain. The accumulation of the L-5-methyltetrahydrofolate in the recombinant strain in a final fermentation product is remarkably higher than that of the original strain, the utilization rate of the raw material is increased, and production cost and energy consumption are reduced.

The invention discloses a serine hydroxymethyltransferase mutant with an amino acid sequence shown in the formula of SEQ ID NO: 3. Compared with wild serine hydroxymethyltransferase, the serine hydroxymethyltransferase mutant has the advantages that the enzyme activity of catalyzing glycine and formaldehyde to react to produce serine is improved, and the serine hydroxymethyltransferase mutant hasindustrial development and application prospects.

The invention provides a nucleoside high-yielding strain as well as a construction method and application thereof. The invention also provides a method for producing nucleoside by fermentation. The method comprises the following steps of (1) enhancing a serine hydroxymethyltransferase gene glyA, as shown in SEQ ID NO:2, of bacillus subtilis; and/or (2) weakening a 2,3-diphosphoglyceric acid independent phosphoglyceric acid mutant enzyme gene pgm of a coded NCBI reference sequence WP_003228330.1 on a chromosome of the bacillus subtilis; and (3) applying the strain obtained in the step (1) and/or the step (2) to fermentation production of the nucleoside. The engineered strain bacillus subtilis provided by the invention is the nucleoside high-yielding strain, can effectively accumulate the nucleoside, improves the yield of the nucleoside, and lays a foundation for industrial production of the nucleoside.

The invention discloses a serine hydroxymethyltransferase gene promoter region methylation degree detection kit. The detection kit comprises DNA extract, a fluorescence quantitative PCR reaction solution, a positive control, a negative control and a plurality of seal pipes with covers. The fluorescence quantitative PCR reaction solution comprises a pair of serine hydroxymethyltransferase gene promoter region methylation specific amplification primers shown in the formulas of SEQ ID NO. 1 and SEQ ID NO. 2. The invention also discloses a method for detecting a serine hydroxymethyltransferase gene promoter region methylation degree. The kit utilizes a fluorescence quantitative PCR technology, has the advantages of real-time monitoring, strong specificity and accurate quantification and ensures the accuracy of the diagnosis result.

The invention discloses a silk antibacterial finishing method based on enzyme-catalyzed conversion and grafting. Glycine in protein fiber macromolecules is catalyzed by utilizing serine hydroxymethyltransferase to be converted into serine, the number of serine in silk fibers can be increased, then the serine in the silk fibers is catalytically oxidized by utilizing laccase and a 2,2,6,6-tetramethyl pyridine-nitrogen-oxide (TEMPO) system to generate an aldehyde group, the aldehyde group is cross-linked with polylysine to perform the silk antibacterial finishing treatment. The silk antibacterial finishing method comprises the following steps: (1) enzymatically converting amino acid in silk; and (2) catalytically oxidizing silk grafted polylysine by virtue of laccase-TEMPO. Compared with thetraditional chemical cross-linking method antibacterial finishing treatment, the silk treated in the method of the invention has good antibacterial performance, mild enzyme treatment condition, and higher physical and mechanical properties compared with an un-treated sample.

Disclosed are methods and pharmaceutical compositions for treating cancer. It was hypothesized that low activity of serine hydroxymethyl transferase (SHMT) due to poor pyridoxal 5′-phosphate (PLP) availability within cancer cells would result in insufficient growth inhibition in cancer cells exposed to 5-fluorouracil (FUra), as well as to FUra in combination with N5-formyl tetra hydro pteroylglutamate (5-HCO—H4PteGlu; folinic acid). Cancer cell lines were exposed to FUra as a single agent and to FUra with folinic acid, in combination with high concentration PLP. There was demonstrated synergistic and additive interactions upon cytotoxicity of FUra by folinic acid and PLP combined in HT29, HCT116, and L1210 cancer cells. Murine studies of parenteral administration of pyridoxamine or pyridoxine in high doses showed that intracellular PLP is augmented to levels close or greater than the Kd reported for binding of cofactor to SHMT, suggesting modulation of the fluoropyrimidines by vitamin B6 was possible.

The invention discloses a double expression application of Arabidopis thaliana serine hydroxymethyltransferase gene and formate dehydrogenase gene. The cDNA of Arabidopis thaliana serine hydroxymethyltransferase SHMT gene is used to construct a plant expression vector, the plant expression vector constructed by the cDNA of Arabidopis thaliana serine hydroxymethyltransferase SHMT gene is transferred to tobacco through Agrobacterium mediation, and a plant expression vector constructed by the cDNA of Arabidopis thaliana formate dehydrogenase FDH gene is transferred to the tobacco through Agrobacterium mediation after detection correctness to obtain two exogenous genes SHMT/FDH inserted double expression transgenic tobacco capable of improving the formaldehyde absorption and tolerance ability of plants. Experiment results show that the double expression transgenic tobacco can change the content of chlorophyll and soluble sugar in tobacco to effectively reduce the toxicity of HCHO to plants in order to make the transgenic tobacco leaf maintain good HCHO absorption ability under the stress of high concentration HCHO; and the double expression transgenic tobacco can effectively reduce the oxidation stress and has a substantially better oxidation stress reduction effect than single expression transgenic tobacco.

The invention relates to a genetically engineered bacterium for producing L-methionine at high yield as well as a construction method and application of the genetically engineered bacterium. According to the invention, an L-methionine synthesis network of escherichia coli is modified, and the utilization capacity of escherichia coli on methylenetetrahydrofolic acid is enhanced by enhancing metF and GCV in a carbon module of an escherichia coli-L-methionine synthesis pathway; by replacing original promoters of fliY and malY with a Trc promoter derived from pTrc99A, a cysteine/cystine internal transport pathway and a cysteine utilization pathway are enhanced, and metabolic inhibition of escherichia coli caused by cysteine generation is relieved; and by knocking out glyA of escherichia coli and introducing glyA derived from Arthrobacter sp.FB24 for overexpression on plasmids, limitation of serine hydroxymethyltransferase of large intestines is relieved, finally, high-yield bacterium containing plasmids is obtained, and the yield of L-methionine is increased to 3.83 g/L from 2.8 g/L.

A transgenic crop plant transformed by a Serine Hydroxymethyltransferase-Like Stress-Related Polypeptide (SHSRP) coding nucleic acid, wherein expression of the nucleic acid sequence in the crop plant results in the plant's increased root growth, and/or increased yield, and/or increased tolerance to environmental stress as compared to a wild type variety of the plant Also provided are agricultural products, including seeds, produced by the transgenic crop plants. Also provided are isolated novel SHSRPs, and isolated novel nucleic acids encoding SHSRPs, and vectors and transgenic plant containing the same.

The invention discloses a method for screening a folic acid metabolism related drug. The method comprises the following steps: (1) mixing a cell line with stable physiological state and a compound tobe detected at different concentrations respectively, wherein the cell line has a serine hydroxymethyltransferase expression function; (2) adding stable isotope labeled serine and incubating until thereaction is complete; 3, obtaining the supernatant of the cell culture solution and detecting the content of glycine label by the stable isotope; (4) judging the activity of the compound to be detected by using the glycine content and the corresponding concentration of the compound to be detected. The screening success rate of the detection method is high, and the screened compounds have strongerefficacy and less side effects.

The invention relates to reconstructed butyric acid bacillus methylophilus for assimilating methanol by utilizing a WLP (White Like Prescription) pathway and a reductive glycine pathway and application thereof. The step of reconstructing the methyl butyric acid bacillus comprises assimilating methanol through a natural WLP way; gene introduced into the reconstructed butyric acid methyl bacillus comprises glycine splitting system aminomethyltransferase (GcvT), glycine splitting system H protein (GcvH), glycine decarboxylase (GcvP) and over-expression endogenous serine hydroxymethyltransferase (glyA) which are derived from escherichia coli. Fermentation verification shows that compared with an original strain, the reconstructed bacillus methylophilus has the advantages that the maximum biomass is increased by 55.26%, the methanol assimilation amount is increased by 34.47%, fermentation conditions for fermentation production and synthesis of butyric acid by the reconstructed strain are optimized, the final maximum biomass is increased by 55.26%, the methanol assimilation amount is increased by 57.14%, and the butyric acid synthesis amount is increased by 77.78%.