26 results about "Benzylisoquinoline" patented technology

The invention discloses a demethylase ODM gene for synthesizing benzylisoquinoline alkaloids and application thereof, the demethylase ODM gene is an ODM1 gene or an ODM2 gene, the nucleotide sequence of the CDS region of the ODM1 gene is shown as SEQ ID NO: 1, and the nucleotide sequence of the CDS region of the ODM2 gene is shown as SEQ ID NO: 2. Aiming at the current situation that the research basis of a key gene for synthesizing corydalmine in rhizoma corydalis is weak, the ODM1 gene for catalyzing tetrahydropalmatine demethylation to specifically generate corydalmine and tetrahydrojatrorrhizine and the ODM2 gene for specifically generating tetrahydrojatrorrhizine are cloned from rhizoma corydalis for the first time. An important theoretical basis is provided for producing the corydalmine by utilizing a synthetic biological method in the future, and the corydalmine mutant has a wide application prospect and a great economic value.

The invention relates to a novel spirobenzylisoquinoline alkaloid hypecoum erectum ketone base C extracted from hypecoum erectum as well as a preparation method and application of the novel spirobenzylisoquinoline alkaloid hypecoum erectum ketone base C, which can be used for effectively extracting and preparing the novel spirobenzylisoquinoline alkaloid hypecoum erectum ketone base C from the hypecoum erectum and realizing the application in preparing a medicine for preventing and treating a non-alcoholic fatty liver disease. Carrying out heating reflux extraction on the dried hypecoum erectum by using ethanol, carrying out acid extraction and alkali precipitation, and sequentially extracting by using chloroform and n-butyl alcohol to obtain an extract of a corresponding part; and mixing the target extract with silica gel, eluting, concentrating under reduced pressure, detecting, combining the same fractions, eluting on a column, mixing the silica gel with the sample, eluting, collecting the fractions with retention time, concentrating and drying to obtain the anise keto alkali C. The invention also discloses a preparation method of the anise keto alkali C. The invention also discloses a preparation method of the anise keto alkali C. The compound can significantly improve free fatty acid-induced HepG2 cell lipid metabolism disorder and lipid accumulation, meanwhile alleviate FFA-induced HepG2 cell damage, can be prepared into various drug dosage forms, is convenient and effective in clinical use, has wide development and application prospects, and has significant economic and social benefits.

The invention discloses a recombinant bacterium and an application of the recombinant bacterium in production of bisbenzylisoquinoline alkaloid. According to the recombinant bacterium constructed by the invention, the synthetic route of the bisbenzylisoquinoline alkaloid is divided into four modules for research, and the de novo synthesis of the bisbenzylisoquinoline alkaloid is realized through multiple strategies; wherein the original strain is an IMX581 yeast strain. Experiments prove that the engineering strain constructed by the invention can be used for efficiently producing the bisbenzylisoquinoline alkaloids, such as (R, S)-actinodaphne, Bisnoraromoline, Bisnoramegine, isotetrandrine, Obaberine and the like, and can be used for efficiently producing the bisbenzylisoquinoline alkaloids, such as the (R, S)-actinodaphne, the Bisnoramegine, the isotetrandrine and the like. The method has an important application value.

The invention discloses a CYP450 enzyme CYP80Q4 participating in biological synthesis of stephania tetrandra alkaloid and application of the CYP450 enzyme CYP80Q4. According to the technical scheme, the cytochrome P450 enzyme from stephania tetrandra is applied to catalysis of a C-O coupling reaction of a compound to generate bisbenzylisoquinoline alkaloid, the name of the protein is CYP80Q4, and the amino acid sequence is a sequence 2 in a sequence table. After a CYP80Q4 gene is expressed in yeast, a microsome extracting solution containing CYP80Q4 protein is extracted, substrates are screened through a substrate spectrum enzymatic reaction, and 10 groups of obtained substrates can be subjected to a C-O coupling reaction under the catalysis of CYP80Q4 enzyme to generate the bisbenzylisoquinoline alkaloid. The method can be applied to the biosynthesis of the dibenzylisoquinoline alkaloid and / or the effective component tetrandrine of the stephania tetrandra, and the breeding of the stephania tetrandra.

Disclosed herein are methods useful for the synthesis of benzylisoquinoline alkaloids ("BIA"), such as alkaloid morphinans. The disclosed methods can be used to produce thebaine, eastern papaverine, codeine, morphine, oxycodone, hydrocodone, oxymorphinone, hydromorphinone, naltrexone, naloxone, hydroxycodeinone, neolpinone, and / or buprenorphine.

The invention discloses a benzylisoquinoline alkaloid glycoside compound as well as a preparation method and application thereof. The preparation method comprises the following steps: soaking tubers of rhizoma corydalis in a 6% acetic acid solution, crushing, soaking in water, and carrying out ultrasonic extraction to obtain a plant extract; after water dispersion, carrying out HPD100 type macroporous resin column chromatography separation, carrying out gradient elution by using ethanol aqueous solutions with different concentrations, and collecting a 50% ethanol elution part to obtain an elution part YH-D; carrying out MCI column chromatography separation, and carrying out gradient elution by using a 0-100% methanol-water solution to obtain four parts of eluents; the preparation method comprises the following steps: dissolving YH-D-2 in water, filtering, and carrying out medium-pressure ODS column chromatography separation, Sephadex LH-20 column chromatography separation, medium-pressure ODS column chromatography separation and semi-preparative C18 column HPLC (High Performance Liquid Chromatography) purification on the filtrate to obtain six new compounds 1-6. In-vitro experiments prove that the elution part YH-D-2 containing benzylisoquinoline alkaloid glycoside of the benzylisoquinoline alkaloid glycoside compounds 1-6 has NO generation inhibition activity, and has a good development prospect as an anti-inflammatory drug.

The application relates to the application of a bisbenzylisoquinoline compound or an analogue thereof and / or pacritinib in the preparation of a medicament for activating TFEB to prevent and / or treat obesity and insulin resistance related diseases. The compound is used for preventing and / or treating obesity or insulin resistance related diseases of an individual in the application of a TFEB agonist in the treatment of obesity and insulin resistance medicament; wherein R1 and R2 are each independently H or methyl; R3, R4, R5 and R6 are each independently 1, 2 or 3 substituents substituted at any position on the corresponding benzene ring, and each of the substituents is independently selected from -OH or -OCH3; the compound promotes the nuclear translocation of TFEB by activating TFEB in adipose tissue macrophages, and then up-regulates the expression of vascular endothelial growth factor A (VEGFA) to promote adipose tissue angiogenesis, thereby relieving obesity and obesity-induced insulin resistance and adipose fibrosis.

Disclosed herein are methods that may be used for the synthesis of benzylisoquinoline alkaloids (“BIAs”) such as alkaloid morphinan. The methods disclosed can be used to produce thebaine, oripavine, codeine, morphine, oxycodone, hydrocodone, oxymorphone, hydromorphone, naltrexone, naloxone, hydroxycodeinone, neopinone, and / or buprenorphine. Compositions and organisms useful for the synthesis of BIAs, including thebaine synthesis polypeptides, purine permeases, and polynucleotides encoding the same, are provided.

The invention discloses methyltransferase, a biological material related to the methyltransferase and application of the methyltransferase in preparation of bisbenzylisoquinoline alkaloid. The methyltransferase disclosed by the invention is StB2 'NMT1, StB7OMT, StB2' NMT2 and StB2NMT, and the sequences of the StB2 'NMT1, the StB7OMT, the StB2' NMT2 and the StB2NMT are respectively shown as SEQ ID No.4, SEQ ID No.6, SEQ ID No.8 and SEQ ID No.10 in a sequence table. The methyltransferase disclosed by the invention can be used for producing isotetrandrine with StBOMT as shown in SEQ ID No.2 and CYP82BC4 as shown in SEQ ID No.13 by taking (R, S)-lindoldhamine as a substrate, and the isotetrandrine can be produced by the methyltransferase, the StBOMT as shown in SEQ ID No.2 and the CYP82BC4 as shown in SEQ ID No.3.

A method for producing berberine or a glycosylated derivative thereof and use thereof. In view of the characteristics of a plant chassis, a new method for detecting endogenous tyrosine in a plant is established, and a compound library for rapidly screening benzylisoquinoline alkaloids and derivatives thereof is established. On this basis, an effective target for enhancing the supply of endogenous tyrosine is obtained by screening, and for the first time, the synthesis of berberine and the glycosylated derivative thereof is achieved in Nicotiana plants, thereby providing a new way for industrial production of berberine compounds. Moreover, the glycosylated derivative can improve the bioavailability of berberine, which is of great significance for the research and development of new drugs.

Disclosed herein are methods that may be used for the synthesis of benzylisoquinoline alkaloids (“BIAs”) such as alkaloid morphinan. The methods disclosed can be used to produce thebaine, oripavine, codeine, morphine, oxycodone, hydrocodone, oxymorphone, hydromorphone, naltrexone, naloxone, hydroxycodeinone, neopinone, and / or buprenorphine. Compositions and organisms useful for the synthesis of BIAs, including thebaine synthesis polypeptides, purine permeases, and polynucleotides encoding the same, are provided.

The present application relates to the technical field of plant genetic engineering, and specifically discloses a benzylisoquinoline alkaloid and derivative synthesis gene AcNMT3, a protein, an application, and a screening method. The screening method of the present application can accurately and effectively screen out the coding gene of nitrogen methyltransferase AcNMT3 in the synthesis pathway of the benzylisoquinoline alkaloid and derivative aristolochic acid of aristolochia contorta, and determine the encoded protein and function. AcNMT3 has the functions of catalyzing nornuciferine to generate N-methylnornuciferine, catalyzing nuciferine to generate N-methylnuciferine, catalyzing 3'-hydroxynuciferine to generate 3'-hydroxy-N-methylnuciferine, catalyzing N-methylnuciferine to generate magnoflorine, and catalyzing laurifoline to generate fujimorine, wherein the conversion efficiency of the secondary amine nitrogen to the tertiary amine nitrogen is the highest, so the main function is AcCNMT. The present application discloses one of the key enzymes in the synthesis of the benzylisoquinoline alkaloid of aristolochia contorta, and lays a foundation for the analysis of the biosynthesis pathway of the benzylisoquinoline alkaloid and derivative, the biosynthesis of the medicinal components, and the molecular breeding of aristolochia contorta.

The present invention discloses bis(benzylisoquinoline) alkaloid compounds, their synthesis, a combination and composition for activity against TLR4 receptors. The compounds of the present invention also show synergistic effect with other antibiotics.

A novel spirobenzylisoquinoline alkaloid anisone C extracted from anise, as well as its preparation method and application, can effectively solve the problem of extracting and preparing the novel spirobenzylisoquinoline alkaloid anisone C from anise, and realize its application in the preparation of drugs for the prevention and treatment of non-alcoholic fatty liver disease. Dried anise is extracted with ethanol by heating and refluxing, followed by acid extraction and alkali precipitation, and sequentially extracted with chloroform and n-butanol to obtain an extract of the corresponding parts. The target extract is mixed with silica gel, eluted, concentrated under reduced pressure, and identified. Fractions of the same size are combined, loaded onto a column, eluted, mixed with silica gel, eluted, and fractions with the same retention time are collected, concentrated, and dried to obtain anisone C. This compound can significantly improve lipid metabolism disorders and lipid accumulation in HepG2 cells induced by free fatty acids, while also reducing FFA-induced HepG2 cell damage. It can be prepared into a variety of pharmaceutical dosage forms for convenient and effective clinical use, with broad development and application prospects and significant economic and social benefits.

The invention provides a benzyl isoquinoline alkaloid yarrowia lipolytica production strain and application thereof.The benzyl isoquinoline alkaloid yarrowia lipolytica production strain is a strain finally obtained through heterologous expression of CYP76AD5, DODC, NCS35, 6 'OMT, CNMT, NMCH and 4' OMT, deletion of HPPD, COMT, ADH2 and PAR4 genes and overexpression of ARO1, ARO2, Aro4K221L, Aro7G139S and ARO10, has the potential of being used as a microbial cell factory for producing BIA, and can be used as a microbial cell factory for producing BIA. (S)-higenamine and (S)-phylline can be synthesized from the beginning under the aerobic condition by using the YPD culture medium, and the synthesis efficiency and yield are remarkably improved.

To provide host cells engineered to produce benzylisoquinoline alkaloids (BIAs), and methods of making and using the same.SOLUTION: A host cell that produces a BIA compound or a precursor thereof, wherein the host cell comprises multiple copies of one or more heterologous coding sequences for one or more enzymes obtained from a different biological source as compared to the host cell. Includes heterologous coding sequences for various enzymes involved in the host cell's synthetic pathways from starting compounds to BIAs. Also, methods of producing BIAs of interest by culturing host cells under culture conditions that promote expression of the enzymes encoded by the heterologous coding sequences of the host cells.SELECTED DRAWING: Figure 4

A method of epimerizing an (S)-1-benzylisoquinoline alkaloid to an (R)-1-benzylisoquinoline alkaloid is provided. The method comprises contacting the (S)-1-benzylisoquinoline alkaloid with at least one enzyme. Contacting the (S)-1-benzylisoquinoline alkaloid with the at least one enzyme converts the (S)-1-benzylisoquinoline alkaloid to an (R)-1-benzylisoquinoline alkaloid.

The application discloses a demethylase ODM gene for synthesizing benzyl isoquinoline alkaloids and application thereof, and the demethylase ODM gene is an ODM4 gene or an ODM5 gene, the CDS region nucleotide sequence of the ODM4 gene is shown as SEQ ID NO:1, and the CDS region nucleotide sequence of the ODM5 gene is shown as SEQ ID NO:2. In view of the fact that the research foundation for key genes for synthesizing corydaline in Corydalis tuber is weak, the ODM4 gene for catalyzing the demethylation of tetrahydropalmatine to specifically generate corydaline and tetrahydrojatrorrhizine and the ODM5 gene for specifically generating tetrahydrojatrorrhizine are cloned from the Corydalis tuber for the first time. The application provides an important theoretical basis for producing corydaline by using a synthetic biology method in the future, and has wide application prospect and great economic value.

The present invention provides pharmaceutical compositions and methods of use of bisbenzylisoquinoline, e.g., 6,6',7,12-tetramethoxy-2,2'-dimethyl-berbaman, and analogs, derivatives, isomers, and modified forms of the compound, e.g., in crystalline, salt, or salt form, in combination with pharmaceutically acceptable acids or other agents, for the treatment of acute, chronic, and preleukemic conditions, as well as lymphoma and solid tumors. These include, but are not limited to, preneoplastic and neoplastic diseases and solid tumors, such as acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL), chronic myeloid leukemia (CML), atypical chronic myeloid leukemia (aCML), and acute myeloid leukemia (AML), polycythemia vera (PV), chronic lymphoblastic leukemia (CLL), myeloproliferative syndrome (MPS), myelodysplastic syndrome (MDS), myeloproliferative neoplasm (MPN), myelofibrosis (MF), and polycythemia vera (PV).

To provide a method of epimerizing an (S)-1-benzylisoquinoline alkaloid to an (R)-1-benzylisoquinoline alkaloid.SOLUTION: The method comprises contacting the (S)-1-benzylisoquinoline alkaloid with at least one enzyme. Contacting the (S)-1-benzylisoquinoline alkaloid with the at least one enzyme converts the (S)-1-benzylisoquinoline alkaloid to an (R)-1-benzylisoquinoline alkaloid.SELECTED DRAWING: Figure 3

The invention provides a method for producing berberine or a glycosylated derivative thereof and application of the berberine or the glycosylated derivative thereof. In combination with the characteristics of plant chassis, a novel method for detecting plant endogenous tyrosine is established, a compound library for rapidly screening benzylisoquinoline alkaloid and derivatives thereof is established, and an effective target for strengthening endogenous tyrosine supply is screened on the basis of the compound library. The synthesis of the berberine and the glycosylated derivative thereof in the Nicotiana plants is realized for the first time, a new way is provided for industrial production of berberine compounds, and the glycosylated derivative can improve the bioavailability of the berberine and has important significance for research and development of new drugs.

The invention discloses a hydroxylase involved in the biosynthesis of benzylisoquinoline alkaloids and its application, and relates to the field of medicinal plant genetic engineering, wherein the amino acid sequence is SEQ ID NO.1, or a protein having hydroxylase function obtained by substitution and / or deletion and / or addition of one or more amino acid residues thereof; or a protein having 90% or more identity therewith and having the function of hydroxylating benzylisoquinoline alkaloids; a recombinant expression vector, a recombinant microorganism; a yeast system composed of the enzyme and a reductase StCPR, and the application of the hydroxylase and its recombinant expression vector in the in vitro synthesis of heterologously expressed StCYP80B protein, and the in vivo synthesis of benzylisoquinoline compounds by recombinant microorganisms and the yeast system. The hydroxylase StCYP80B provided by the invention expands the substrate recognition range and is an effective enzymatic tool for hydroxylating monobenzylisoquinoline alkaloids of different structures.

The invention discloses a novel benzylisoquinoline compound as well as a pharmaceutical composition and application thereof, and particularly provides a compound V as well as pharmaceutically acceptable salts, solvates, metabolites, tautomers or prodrugs thereof. The compound V comprises a compound shown in the formula I and pharmaceutically acceptable anions. The compound provided by the invention is relatively good in drug effect and good in application prospect.

The invention discloses an enzyme related to biosynthesis of an effective component of a traditional Chinese medicine radix stephaniae tetrandrae as well as a biological material and application thereof. According to the technical scheme, the cytochrome P450 enzyme from stephania tetrandra is applied to catalysis of a C-O coupling reaction of bisbenzylisoquinoline alkaloid to generate cyclized bisbenzylisoquinoline alkaloid, the name of the protein is CYP82BC3, and the amino acid sequence of the protein is a sequence 2 in a sequence table. According to the invention, microsome extracting solutions of CYP82BC3 and CYP80Q4 proteins are extracted to carry out three groups of substrate enzymatic reactions, and compared with a CYP80Q4 enzyme independent catalytic reaction, the CYP82BC3 can catalyze a catalytic product of the CYP80Q4 enzyme to continuously carry out cyclization so as to generate the cyclized bisbenzylisoquinoline alkaloid. The method can be applied to biosynthesis of cyclized bisbenzylisoquinoline alkaloid and / or an effective component tetrandrine of stephania tetrandra and breeding of stephania tetrandra.

The present application relates to a kind of from Bauhinia championii single benzyl isoquinoline alkaloid and its preparation method and application and pharmaceutical composition, the compound is tested to show certain pharmacological activity by opioid delta receptor target point, can be used in the drug development for preventing and / or treating pain and other diseases.The compound structure

A method of demethylizing an opioid to a nor-opioid is provided. The method comprises contacting an opioid with at least one enzyme. Contacting the opioid with the at least one enzyme converts the opioid to a nor-opioid. A method of converting a nor-opioid to a nal-opioid is provided. The method comprises contacting a nor-opioid with at least one enzyme. Contacting the nor-opioid with the at least one enzyme converts the nor-opioid to a nal-opioid.