17 results about "Efflux" patented technology

The application belongs to the technical field of pharmaceutical chemistry, and particularly relates to a pyrimidine and thienopyrimidine derivative, a preparation method and application thereof. The pyrimidine derivative in the application is a compound with the structure of formula I, and the thienopyrimidine derivative is a compound with the structure of formula II. The pyrimidine and thienopyrimidine derivative can be used as an AcrB efflux pump inhibitor, and can significantly enhance the antibacterial activity when combined with an antibacterial drug. The Nile red experiment shows that the compound 64c can completely inhibit the AcrB-mediated efflux at a concentration of 50 μM, and the effect is better than that of the positive control PA beta N. The compound in the application has novel structure and excellent activity, and can be used for preparing an AcrB efflux pump inhibitor for reversing bacterial drug resistance and an antibacterial sensitizing drug.

The application provides an engineered oxytetracycline-producing bacterium and a construction method and application thereof. The application takes Streptomyces albus Del14 as a chassis production strain, and successfully expresses an otc cluster in S.albus Del14 for the first time through heterologous reconstitution. Specifically, the otc cluster is expressed by increasing one copy of otcR started by a strong promoter PkasO*; the efflux of OTC is improved by knocking out a negative regulatory factor OtrR in the cluster to release the repression on otrB; further, an efficient OTC production chassis Del14B::oxy1KΔotrR is screened out by replacing an integrase site, and the OTC yield of the chassis Del14B::oxy1KΔotrR reaches 1.1 g / L on the 6th day, which is equivalent to the yield of the original production strain S.rimosus M4018 on the 8th day, so that the heterologous efficient synthesis of OTC is realized.

This invention provides an engineered bacterium for producing ectoine, its preparation method, and its application. The engineered bacterium is prepared using a method comprising the following steps: using *Corynebacterium glutamicum* as the starting strain, feedback inhibition by aspartate kinase LysC is relieved, the activity of the gene lysE encoding lysine efflux permease is reduced, and the ectoine synthesis gene cluster ectABC is expressed. Based on this, the activity of any one or at least two of the following—diaminobutyrate acetyltransferase EctA, pyruvate carboxylase Pyc, or aspartate kinase LysC—is enhanced, and / or the activity of any one or at least two of the following—maloquinone oxidoreductase Mqo or homoserine dehydrogenase Hom—is reduced to further increase ectoine yield.

The invention discloses a parameterized constraint system and method for efflux pump avoidance and off-target risk inhibition, which are applied to the field of biological medicines, and aims to solve the dual problem that toxic risks are caused by efflux pump mediated drug resistance enhancement and off-target combination of existing antibacterial drugs. The method comprises the following steps: constructing an efflux pump identification avoidance five-dimensional feature space and a target spot specificity geometric-electrical constraint boundary, performing structure mapping and deviation degree evaluation on candidate molecules, and triggering directional modification; the target matching is verified through molecular docking, and if the target does not reach the standard, the pharmacophore is locally adjusted; virtual screening is carried out based on an off-target protein database, a secondary structure disturbance mechanism is started for high-risk molecules, and a stereoisomerism or electrical reversal group is introduced to destroy non-target binding; according to the method, collaborative optimization of antibacterial efficacy, drug resistance avoidance and safety risk is achieved, and the research and development efficiency and druggability of candidate molecules are remarkably improved.

The application discloses application of tegaserod maleate in preparation of an antibacterial drug synergist, and proves that the tegaserod maleate can produce a synergistic antibacterial effect with a plurality of commonly used antibacterial drugs (including tylosin, tetracycline, enrofloxacin, ampicillin and the like), can significantly enhance the antibacterial activity of the antibacterial drugs on gram-negative bacteria, and reduce the drug resistance of bacteria to the antibacterial drugs; the antibacterial composition composed of the tegaserod maleate and the antibacterial drugs can be used for preparing a drug for treating escherichia coli infection, and the synergistic antibacterial mechanism is mainly to destroy the inner and outer membrane permeability of bacteria, regulate the proton motive force of bacteria, inhibit the activity of bacterial efflux pumps, interfere with the energy metabolism homeostasis of bacteria and induce the bacteria to produce oxidative stress. The application provides a new technical strategy for the treatment of clinical escherichia coli infection, and has important clinical application value and industrialization potential.

This invention discloses a genetically engineered bacterium producing high levels of L-homoserine, its construction method, and its applications, belonging to the field of biotechnology. The genetically engineered bacterium uses *Escherichia coli* W3110 as the substrate cell. By knocking out the metA, lysA, thrBC, pflB, ldhA, poxB, adhE, iclR, sthA, tdcC, lacI, and ptsG genes, and replacing the promoters of ppc, aspC, and gdhA genes with the inducible strong promoter Ptrc, and by performing site-directed mutagenesis on the thrA and asd genes, and simultaneously overexpressing the thrA*, pnhsd, asd, asd*, and rhtA genes using free plasmids, a recombinant strain HOM20 was constructed. This strain, fermented in a 5 L fermenter for 48 h, achieved an L-homoserine yield of 135.4 g / L and a sugar-acid conversion rate of 44%, significantly superior to existing technologies. This invention achieves directional carbon flow allocation, cofactor balance, feedback inhibition removal, and enhanced product efflux through multi-gene synergistic modification, and has broad prospects for industrial application.

This invention belongs to the field of antibacterial nanomaterials, specifically relating to nanoparticles that inhibit methicillin-resistant Staphylococcus aureus (MRSA) resistance. The nanoparticles have a three-layer structure, consisting of a core layer composed of a copper nanoparticle and a copper oxide composite, a mesoporous graphite shell, and a bis(amino)PEG coating, from the inside out. The above method achieves physical encapsulation of copper nanoparticles by graphite using a one-step plasma arc method; and constructs a Cu / Cu₂O interface through precise oxygen-controlled thermal oxidation treatment, while simultaneously achieving effective protection and exposure of the active A layer by mesoporousizing the graphite; the use of bis(amino)PEG to form a polymer coating on the nanoparticles enhances bacterial uptake capacity and improves biocompatibility. The nanoparticles prepared by this invention can increase the utilization rate of drug-resistant bacteria by inhibiting bacterial biofilm structures and efflux pumps that cause bacterial infections, thereby improving the clearance capacity against drug-resistant bacterial infections and demonstrating great potential for application and clinical translation.

This invention provides an engineered bacterium for producing ectoine, its preparation method, and its application. The engineered bacterium is prepared using the following steps: using Corynebacterium glutamicum as the starting strain, feedback inhibition of aspartate kinase LysC is relieved, the activity of the gene lysE encoding lysine efflux permease is reduced, and the ectoine synthesis gene cluster ectABC is expressed; based on this, the activity of any one or at least two combinations of aspartate semialdehyde dehydrogenase Asd, aspartate transaminase AspB, or 6-phosphogluconate dehydrogenase Gnd is enhanced to further increase the yield of ectoine.

This invention belongs to the field of biomedical technology, specifically disclosing an injectable embolic agent, its preparation method, and its application. The embolic agent is a hydrocolloid system containing core-shell structured nanoparticles: the core contains Cu... 2+ Salt and ATOX1 inhibitors, where ATOX1 inhibitors can inhibit copper ion efflux and promote intracellular copper accumulation, and interact with Cu 2+ It synergistically induces copper death in tumor cells; the shell is a thermosensitive block copolymer hydrogel that can interact with Cu. 2+ Coordination bonds are formed, enhancing the stability of nanoparticles, while a sol-gel transition occurs at physiological temperatures, enabling precise vascular embolization; the overall core-shell structure allows for the formation of Cu... 2+ The sustained-release effect of ATOX1 inhibitors was observed. In the VX2 rabbit hepatocellular carcinoma model, this embolization agent significantly improved tumor necrosis rate and reduced metastasis rate compared to traditional iodized oil embolization; it also downregulated hypoxia- and angiogenesis-related factors such as HIF-1α, VEGF, and CD31, inhibited MMP9-mediated tumor invasion and metastasis, and promoted CD8+. + T-cell infiltration effectively improves the tumor immunosuppressive microenvironment after transarterial chemoembolization.

The application relates to the biomedical technology field and discloses application of BAZ2B gene as a target point in inhibition of drug efflux of tumor cells. The application successfully proves for the first time that an inhibitor of the BAZ2B gene or a coded protein has an inhibiting effect on the efflux of nanometer materials such as Au, SiO2 and micelles in cells. The efflux of FB@SR micelle nanometer materials to tumor cells (such as melanoma cells) is reduced by inhibiting the BAZ2B gene, and the boron content in the cells is increased. The FB@SR is used as a new type of boron delivery agent, and compared with cells without BAZ2B gene silencing, the boron content in the cells is increased after the BAZ2B gene is silenced, the BNCT treatment window is prolonged, and better and higher-quality treatment effects are obtained.

This invention relates to a high-yield recombinant cysteine ​​strain, a fermentation method, and their applications. The invention employs a growth-stage-dependent promoter to dynamically regulate the cysteine ​​efflux protein gene. ydeD The expression of the gene was controlled by promoters of varying strengths to regulate the expression of the cysteine ​​efflux protein mutant gene. yfiK G156S / N157S The expression of cysteine ​​was finally knocked out and transferred into the protein gene. yeaN Simultaneously integrate dynamic regulation ydeD Genes were used to construct a high-yield recombinant strain of cysteine, which can produce L-cysteine ​​using glycerol as a carbon source. The yield of L-cysteine ​​in shake flask fermentation reached 9.40 g / L, and the highest yield in batch fermentation reached 38.50 g / L, showing great potential for industrial application.

This invention relates to the field of air disinfection devices, specifically to a composite intelligent circulating air disinfection device and method. The device includes a housing, and within the housing are a gas control device, a liquid control device, a light control device, a photoexcitation device, and a nanoenzyme adsorption device. This invention integrates modules corresponding to four methods: electrochemical strong oxidizing bactericidal liquid disinfection, ultraviolet irradiation disinfection, nanoenzyme disinfection, and photoexcitation disinfection. This enables highly efficient killing of various pathogens in the air, including bacteria, fungi, and viruses. Furthermore, through ultraviolet-assisted electrochemical oxidation technology, it downregulates the expression of bacterial cell wall synthesis genes and efflux pump genes, inhibits energy metabolism, and induces key gene mutations, effectively degrading and inactivating antibiotic resistance genes, blocking the spread of drug resistance. This significantly improves the quality and efficiency of air disinfection while ensuring the coexistence of humans and the machine.

This invention relates to the field of bactericide technology, specifically to a celandine bactericide and its preparation method. The bactericide is composed of the following parts by weight: antibacterial active ingredient: 0.1-0.5 parts; functional microbial agent: 2-20 parts; carrier: 70-90 parts; wherein the antibacterial active ingredient is composed of celandine and N-aryl-3,4-dihydroisoquinoline derivative in a mass ratio of 1:(0.2-5). This application introduces iodine and bromohalogen atoms at specific positions of N-aryl-3,4-dihydroisoquinoline, enabling it to produce a significant synergistic antibacterial effect with celandine. Beneficial bacteria such as Bacillus amyloliquefaciens and Pseudomonas fluorescens can resist the effects of sub-inhibitory drug concentrations by secreting cyclic lipopeptides and upregulating efflux pumps. The technology of encapsulating the antibacterial active ingredient into a sustained-release unit and combining it with a carrier that adsorbs live bacteria significantly improves the retention rate of live bacteria, achieving a long-term balance between stable drug release and beneficial bacterial activity.

The application discloses a biosynthesis gene cluster of marine fungus pyrenophorol compounds and application thereof. The nucleotide sequence of the biosynthesis gene cluster is shown in the 1-18549th of SEQ ID NO. 1, and the biosynthesis gene cluster comprises six genes, i.e. a gene responsible for synthesis of a pyl skeleton structure, namely pylA and pylB; a gene responsible for hydroxylation of carbon 4 and 4' in the pyl, namely pylC; a gene responsible for ketone-enol tautomerism, namely pylE; a gene responsible for reduction of ketone groups at carbon 4 and 4' into hydroxyl groups, namely pylD; and a gene responsible for compound efflux, namely pylF. All the gene information related to pyl biosynthesis provided by the application can help understand the biosynthesis mechanism of the sixteen-membered ring dilactone family natural products, and provide materials and knowledge for further structural modification of the compounds.

Provided are a threonine / homoserine export protein variant, and a method of producing an L-amino acid using the same.

The application belongs to the technical field of antibiotic application, and discloses that microplastics affect the absorption of ciprofloxacin in the intestinal tract through the TLR4 / NF-kappa B pathway regulating P-gp protein. Our research finds that microplastics can activate the expression of P-gp glycoprotein in intestinal epithelial cells through the NF-kappa B pathway in the intestinal tract, thereby reducing the absorption of ciprofloxacin hydrochloride in the intestinal tract, and further affecting the core mechanism of pharmacokinetics and pharmacodynamics of ciprofloxacin hydrochloride in animals. Pyruvate ethyl effectively inhibits the NF-kappa B pathway. The application also finds that after ivermectin inhibits the P-gp glycoprotein of Caco2 cells, the P-gp glycoprotein cannot efflux ciprofloxacin hydrochloride, so that the content of ciprofloxacin hydrochloride in Caco2 cells increases. Therefore, the application also protects the application of ivermectin in preparing a promoter of the content of ciprofloxacin hydrochloride in Caco2 cells incubated with microplastics.

The application provides an engineering strain for constructing high-yield anti-insect immunity cyclic peptide GXP-A based on metabolic engineering and synthetic biology strategies, and the yield of GXP-A is significantly improved from 0.92 mg / L of the wild type to 587.5 mg / L, which is more than 600 times, and has the industrial production potential. The genetic stability of the application is high: through genome simplification and chassis optimization, the genetic background of the strain is clear, and is suitable for long-term fermentation production. The strategy of the application can be popularized: the integrated strategies such as promoter engineering, precursor engineering and efflux engineering can provide reference for the high-yield construction of other microbial natural products, and solve the problems of low yield, high production cost and difficult industrial application of GXP-A in the prior art. Through systematic metabolic engineering modification, the synthesis capacity of GXP-A is significantly improved, and key raw materials are provided for the development of efficient and environmentally friendly biological insecticide synergist.