dTMP imbalance through thymidylate 5'-phosphohydrolase activity induces apoptosis in triple-negative breast cancers.

Immunotherapy has a number of advantages over traditional anti-tumor therapy but can cause severe adverse reactions due to an overactive immune system. In contrast, a novel metabolic treatment approach can induce metabolic vulnerability through multiple cancer cell targets. Here, we show a therapeutic effect by inducing nucleotide imbalance and apoptosis in triple negative breast cancer cells (TNBC), by treating with cytosolic thymidylate 5'-phosphohydrolase (CT).

Pharmacological Activities for L., Focusing on the Immunostimulatory Property from the Fruit Aqueous Extract.

Depending on the extraction method, numerous compounds that have specific pharmacological effects can be obtained from L. There is a growing scientific interest in health problems related to aging. Efforts to develop safe immune-enhancing pharmaceuticals are increasing.

Efficient recovery of recombinant CRM197 expressed as inclusion bodies in E.coli.

CRM197, which retains the same inflammatory and immune-stimulant properties as diphtheria toxin but with reduced toxicity, has been used as a safe carrier in conjugated vaccines. Expression of recombinant CRM197 in E. coli is limited due to formation of inclusion bodies.

Activation of macrophage mediated host defense against by L.

Background: The innate immune system plays a crucial role in the initiation and subsequent direction of adaptive immune responses, as well as in the removal of pathogens that have been targeted by an adaptive immune response.

Objective: L. was reported to have immunostimulatory properties that might protect against infectious diseases.

Rational modification of substrate binding site by structure-based engineering of a cellobiose 2-epimerase in Caldicellulosiruptor saccharolyticus.

Background: Lactulose, a synthetic disaccharide, has received increasing interest due to its role as a prebiotic, specifically proliferating Bifidobacilli and Lactobacilli and enhancing absorption of calcium and magnesium. The use of cellobiose 2-epimerase (CE) is considered an interesting alternative for industrial production of lactulose. CE reversibly converts D-glucose residues into D-mannose residues at the reducing end of unmodified β-1,4-linked oligosaccharides, including β-1,4-mannobiose, cellobiose, and lactose.

Transcriptional profiling of thymidine-producing strain recombineered from Escherichia coli BL21.

DNA microarrays were used to compare the expression profiles of a thymidine overproducing strain (BLT013) and its isogenic parent, Escherichia coli BL21(DE3), when each was grown under well-defined thymidine production conditions with glycerol as carbon source. Here we describe the experimental procedures and methods in detail to reproduce the results and provide resource to be applied to similar engineering approach (available at Gene Expression Omnibus database under GSE69963). Taken together, the microarray data provide a basis for new testable hypotheses regarding enhancement of thymidine productivity and attaining a more complete understanding of nucleotide metabolism in bacteria.

Development of a Novel Plasmid-Free Thymidine Producer by Reprogramming Nucleotide Metabolic Pathways.

A novel thymidine-producing strain of Escherichia coli was prepared by genome recombineering. Eleven genes were deleted by replacement with an expression cassette, and 7 genes were integrated into the genome. The resulting strain, E.

Deoxycytidine production by a metabolically engineered Escherichia coli strain.

Background: Rational engineering studies for deoxycytidine production were initiated due to low intracellular levels and tight regulation. To achieve high-level production of deoxycytidine, a useful precursor of decitabine, genes related to feed-back inhibition as well as the biosynthetic pathway were engineered. Additionally, we predicted the impact of individual gene expression levels on a complex metabolic network by microarray analysis.

Anti-angiogenic effects of resveratrol in combination with 5-fluorouracil on B16 murine melanoma cells.

5-Fluorouracil (5-FU) has been used as a chemotherapeutic drug for various types of cancer, although the development of resistance remains a major limitation for its use in clinical settings. In the present study, the anti-angiogenic effects of resveratrol and 5-FU either alone or in combination were examined in a B16 murine melanoma model. Co-treatment using resveratrol and 5-FU inhibited cell proliferation more efficiently compared with use of either drug alone and the antiproliferative effect coincided with changes in the expression levels of AMP-activated protein kinase (AMPK), cyclooxygenase-2, vasodilator-stimulated phosphoprotein (VASP) and vascular endothelial growth factor (VEGF).

Improved production of isomaltulose by a newly isolated mutant of Serratia sp. cells immobilized in calcium alginate.

Isomaltulose, also known as palatinose, is produced by sucrose isomerase and has been highlighted as a sugar substitute due to a number of advantageous properties. For the massive production of isomaltulose, high resistance to sucrose and stability of sucrose isomerase as well as sucrose conversion yields would be critical factors. We describe a series of screening procedures to isolate the mutant strain of Serratia sp.

Enhancement of thymidine production in E. coli by eliminating repressors regulating the carbamoyl phosphate synthetase operon.

Thymidine is an important precursor in antiviral drugs. We have enhanced thymidine production in E. coli by eliminating the repressors in the transcription of the gene coding for carbamoyl phosphate synthetase.

Improvement of coenzyme Q(10) production by increasing the NADH/NAD(+) ratio in Agrobacterium tumefaciens.

Previously screened CoQ(10)-overproducing Agrobacterium tumefaciens A603-35 showed a relatively high NADH/NAD(+) ratio (1.1), as compared to parental strain C58 (0.2) when we increased the expression levels of NADH-generating enzymes.

Cloning and characterization of the xyl1 gene, encoding an NADH-preferring xylose reductase from Candida parapsilosis, and its functional expression in Candida tropicalis.

Xylose reductase (XR) is a key enzyme in D-xylose metabolism, catalyzing the reduction of D-xylose to xylitol. An NADH-preferring XR was purified to homogeneity from Candida parapsilosis KFCC-10875, and the xyl1 gene encoding a 324-amino-acid polypeptide with a molecular mass of 36,629 Da was subsequently isolated using internal amino acid sequences and 5' and 3' rapid amplification of cDNA ends. The C.

Purification and characterization of a novel mannitol dehydrogenase from a newly isolated strain of Candida magnoliae.

Mannitol biosynthesis in Candida magnoliae HH-01 (KCCM-10252), a yeast strain that is currently used for the industrial production of mannitol, is catalyzed by mannitol dehydrogenase (MDH) (EC 1.1.1.

Fumarate-mediated inhibition of erythrose reductase, a key enzyme for erythritol production by Torula corallina.

Torula corallina, a strain presently being used for the industrial production of erythritol, has the highest erythritol yield ever reported for an erythritol-producing microorganism. The increased production of erythritol by Torula corallina with trace elements such as Cu(2+) has been thoroughly reported, but the mechanism by which Cu(2+) increases the production of erythritol has not been studied. This study demonstrated that supplemental Cu(2+) enhanced the production of erythritol, while it significantly decreased the production of a major by-product that accumulates during erythritol fermentation, which was identified as fumarate by instrumental analyses.