57 results about "Biosynthetic genes" patented technology

The invention discloses a saccharomyces cerevisiae recombinant strain based on a uracil metabolism gene URA3 as well as a construction method and application of the saccharomyces cerevisiae recombinant strain. The construction method comprises the following steps: taking saccharomyces cerevisiae rich in farnesyl pyrophosphate as an original strain, introducing a uracil metabolism gene URA3, synchronously overexpressing a ribosome biosynthetic gene UTP10 and an iron metabolism gene FIT3, and utilizing the uracil metabolism gene URA3 to express up-regulation correlation with the ribosome biosynthetic gene UTP10 and the iron metabolism gene FIT3, so as to obtain the farnesyl pyrophosphate-rich saccharomyces cerevisiae. The metabolic flux of the terpenoids is enhanced, and the saccharomyces cerevisiae recombinant strain for efficiently producing the terpenoids is constructed. According to the method, a metabolic network of yeast is systematically optimized, and combined regulation and control on precursor flux distribution, protein translation capability and metal ion steady state are realized, so that the microbial synthesis efficiency of sesquiterpenoids such as patchouli alcohol and beta-elemene is remarkably improved.

This invention discloses a *Bacillus laterosporus* strain for the stable production of nonribosomal cyclic lipolipeptide and its construction method. The M1A gene in the Bogorol biosynthetic gene cluster is knocked out using CRISPR-Cas9 technology to block the Bogorol pathway, which competes with Brevicidine for substrates. Subsequently, the pMCCas9-S48 plasmid, which integrates S8 and S41 sgRNAs and their homologous arms as repair templates, is used to simultaneously knock out S8 and S41 family peptidase genes, preventing the expression of extracellular degradation enzymes. This invention also provides the application of the above strain in the preparation of nonribosomal cyclic lipolipeptide of Brevicidine and a method for preparing the nonribosomal cyclic lipolipeptide. This strain, through reducing metabolic competition and preventing product degradation, exhibits rapid cell growth, stable production of Brevicidine, and significantly reduced degradation rate, resulting in a 66.13% increase in fermentation yield compared to the unmodified strain. This invention solves the problems of degradation and unstable yield in the production of Brevicidine, provides an effective technical approach for the industrial production of Brevicidine, and provides important technical support for the development and application of novel antimicrobial peptide drugs.

The present application belongs to the field of biotechnology, and particularly relates to a biosynthesis gene cluster of fungal polyketide compounds and application thereof. The present application provides a heterologous expression method of an aspertaichunol compound biosynthesis gene combination, and a compound aspertaichunol B is obtained through the method, and a compound aspertaichunol A is prepared through acid hydrolysis of the aspertaichunol B, which has important significance for future research and development of an efficient biosynthesis method for preparing the aspertaichunol compound.

Methods for identifying biosynthetic gene clusters that include genes for producing compounds that interact with specific target proteins are disclosed. Some methods relate to bioinformatics methods for identifying and / or prioritizing biosynthetic gene clusters. Related systems, components, and tools for the identification and expression of such gene clusters are also disclosed.

The application discloses a gene combination for biosynthesis of paclitaxel and application thereof, and relates to the technical field of genetic engineering. The application breaks through the limitation of traditional paclitaxel extraction and synthesis technology, and for the first time adopts a transformation method of Physcomitrella patens to perform multi-gene co-expression on a paclitaxel synthesis pathway. The application has wider gene source compatibility, and opens up a brand-new technical path for paclitaxel synthesis. As a model plant, the Physcomitrella patens has the characteristics of rapid growth and easy cultivation. After a specific gene combination is introduced into the Physcomitrella patens, a metabolic pathway related to paclitaxel synthesis in the Physcomitrella patens cells can be fully activated, and the Physcomitrella patens is prompted to efficiently synthesize paclitaxel.

The invention discloses a 5 / 8 / 5 chitosan clostridium diterpenoid compound, a biosynthetic gene cluster and application of the biosynthetic gene cluster, and relates to the technical field of biological medicines. A 5 / 8 / 5 chitin type diterpenoid biosynthetic gene cluster Thm in trichoderma harzianum is identified through a genome mining system, chitin diterpenoid compounds with diversified structures are obtained by means of heterologous expression, the obtained compounds are subjected to anti-thrombotic activity comprehensive evaluation, and the result shows that the compounds 6 and 31 can obviously inhibit vascular thrombosis, the compound 6 has a remarkable inhibition effect on collagen-induced platelet aggregation, and the compound 31 has a better inhibition capability on thrombin-induced platelet activation. The compounds 6 and 31 show powerful antithrombotic effects in artery, vein and pulmonary artery thrombosis models, so that powerful technical support is provided for development of antithrombotic drugs.

The present application relates to a kind of cyclic ester peptide compound aglomycin A biosynthesis gene cluster and its application.The nucleotide sequence of the gene cluster is as shown in SEQ ID NO.1, and the use is to produce peptide compound aglomycin A or peptide compound aglomycin D.

NEW SMALL MOLECULES AND METHODS USING THEM FOR SKIN TREATMENT. The disclosure relates to new biosynthetic gene clusters encoding type II polyketides, their products, extracts and compositions comprising the products, and methods for using the products, extracts, and compositions for skin treatment, e.g., to enhance the skin's barrier function and / or immune defenses. Figure for abstract: none

The present disclosure relates to methods and systems for identifying genes associated with biosynthetic gene clusters (BGCs), including embedded target genes (ETaGs) that are homologs of potential therapeutic targets. The methods and systems described herein apply a comparative genomics and manual review or machine-learning model to analyze grid representations such as heat maps, which assess across a plurality of diverse genomes distribution of orthologs (e.g., bidirectional best hits) of a plurality of query genes that are co- localized with an anchor gene (e.g., a core synthase gene) of a BGC in a query genome.

The invention relates to the technical field of saccharomyces cerevisiae expression foreign protein, and discloses a saccharomyces cerevisiae strain with ASFV p14.5 displayed on the surface and a construction method and application thereof, and the method comprises the following steps: (1) synthesizing a delta site homologous arm sequence; (2) seamlessly connecting the homologous arm sequence of the delta site to a carrier pET23a, connecting a selective marker tryptophan biosynthetic gene TRP1 to the 5'end of the upstream homologous arm sequence of the delta site, and sequentially connecting an Aga2 gene, an E120R gene, a T2A peptide gene and an mCherry gene to the 5 'end; (3) carrying out enzyme digestion on two sides of the delta site through restriction endonuclease salI, and recovering a linearized fragment through agarose gel; and (4) integrating the recovered fragments into a host saccharomyces cerevisiae genome through a chemical conversion method, and culturing until bacterial colonies grow. The surface display type saccharomyces cerevisiae strain obtained by the invention not only has the stability of integrative saccharomyces cerevisiae for expressing foreign protein, but also can be used for more easily and more intuitively screening a high-expression quantity saccharomyces cerevisiae strain by combining the T2A peptide with mCherry.

Recombinant Sorangium cellulosum for producing de-epoxidized epothilone B by fermentation, insertional inactivation of an epoK gene in an epothilone biosynthetic gene cluster in the recombinant bacteria, and a method for producing de-epoxidized epothilone B using the recombinant bacteria.

The application discloses a method for biosynthesis of gene or gene cluster product based on chromatin three-dimensional structure, and belongs to the field of genetic engineering. The method can realize the improvement of the target gene or gene cluster product by the directional integration of the target gene or gene cluster into the strong correlation chromatin region with high frequency interaction on the genome. The method has the characteristics of simple implementation, good repeatability, remarkable effect and the like, and can be widely applied to the improvement of the target gene or gene cluster product.

The application belongs to the field of agricultural biotechnology and microbial engineering technology, and particularly relates to a biosynthesis gene cluster of cystobactamids and application. The nucleotide sequence of the biosynthesis gene cluster is shown as SEQ ID NO:1. The application discloses a novel biological function of cystobactamids except for antibiotics, broadens the application scene, and has a good development prospect in the field of agricultural biological control.

The invention discloses a pear PbrRGL3 gene and application of the pear PbrRGL3 gene. The PbrRGL3 gene which is separated from Dangshan pears and has the effect of inhibiting the formation of pear cell lignin has a nucleotide sequence as shown in SEQ ID No. 1, and an amino acid sequence coded by the PbrRGL3 gene is as shown in SEQ ID No. 2 in a sequence table. The PbrRGL3 gene is subjected to transient overexpression in pear fruits by adopting an agrobacterium transient transformation method, the lignin content of pulp is remarkably reduced, and the expression of a lignin biosynthetic gene is reduced; the effect of silencing the PbrRGL3 gene is opposite to that of silencing the PbrRGL3 gene; an overexpression vector constructed by the gene is introduced into arabidopsis thaliana, the lignin content of inflorescence stems of the obtained PbrRGL3 transgenic arabidopsis thaliana is remarkably reduced, and the lignification degree of conduit cells and vascular intervascular fibrocytes is weakened. Therefore, the PbrRGL3 participates in regulating and controlling the formation of the lignin in the pear fruit stone cells.

The application discloses a biosynthesis gene cluster of a polyene macrolide natural product mandimycin, and a natural product and application of the biosynthesis gene cluster, wherein the nucleotide sequence of the biosynthesis gene cluster is shown as SEQ ID NO. 1, and the compound structural formula of the natural product mandimycin and mandimycin B is shown as formula I and formula II. The natural product mandimycin can target fungal cell membrane phospholipid molecules, especially phosphatidylinositol, cause important ion efflux in fungal cells, and lead to fungal cell death. The natural product mandimycin and mandimycin B have strong in-vivo and in-vitro antibacterial activity and a broad antibacterial spectrum on various WHO-published multiple drug-resistant fungal key pathogens, including candida, aspergillus, cryptococcus, mucor and fusarium.

The invention provides amycolatopsis mediterranei with gene defects as well as a construction method and application of the amycolatopsis mediterranei. The first aspect of the invention provides a construction method of the amycolatopsis mediterranei with the gene defect, and the construction method comprises the step of knocking out a rifamycin biosynthetic gene cluster in a receptor amycolatopsis mediterranei strain U32 (Cas12a) genome and an integrated plasmid pDZLCas12a containing an FnCas12a coding gene to obtain the amycolatopsis mediterranei with the gene defect. According to the invention, a rifamycin biosynthetic gene cluster in a genome of an amycolatopsis mediterranei strain U32 (Cas12a) and an integrated plasmid pDZLCas12a containing an FnCas12a coding gene are knocked out, so that the amycolatopsis mediterranei with gene defects is constructed, and the amycolatopsis mediterranei can be used as a chassis strain for mining identified or unidentified biosynthetic gene clusters in actinomycetes.

The application discloses streptomyces 891-DC with high aurovertin A yield and application thereof. The application uses CRISPR-Cas9 technology to first change an incomplete attB site sequence in the genome of streptomyces 891 into a complete attB site sequence, promote a plasmid containing a target gene chry, an integrase phiC31 gene and an attP site, and improve the integration rate of the target gene through specific combination of the attP site and the attB site on the genome. Secondly, a promoter capable of obviously improving the yield is screened to express the aurovertin biosynthesis gene cluster, so that the more stable and higher-yield streptomyces 891-DC is obtained. The aurovertin A shake flask fermentation yield is 1411.23+ / -29 mg / L, which is 60% higher than that of the original strain, and the genetic stability is good, thereby laying a technical foundation for industrial production of aurovertin.

The present application relates to a kind of antibacterial new skeleton diterpene compound and its synthesis method.The present application obtains a terpene cyclase of unknown function and a P450 oxidase of unknown function from the genomic data disclosed in a strain of Aspergillus fumigatiaffinis CNM-CM8980, by heterologous expression and in vitro enzyme catalytic reaction of Aspergillus oryzae, it is found that the terpene cyclase can be catalyzed to generate a diterpene compound with 6 / 5 / 5 / 5 brand new four-ring skeleton, candidate P450 oxidase can act on the diterpene compound to generate the oxidation product with antibacterial activity.The present application first reports the chemical structure of the diterpene compound, biological activity and biosynthesis gene, on the one hand, provides lead compound resources for discovering new antibiotics, on the other hand, lays a foundation for realizing its green and efficient synthesis.

The invention belongs to the technical field of agricultural biotechnology and microbial engineering, and particularly relates to a biosynthetic gene cluster of cystobactamid compounds and application of the biosynthetic gene cluster. The nucleotide sequence of the biosynthetic gene cluster is as shown in SEQ ID NO: 1. The invention discloses a brand new biological function of the cystobactamid except antibiotics for the first time, broadens the application scene of the cystobactamid, and has a good development prospect in the field of agricultural biological control.

The present disclosure relates to computer-implemented methods and systems for identifying biosynthetic gene clusters (BGCs) that encode pathways for the production of secondary metabolites. Secondary metabolites that target genes or gene products that are homologous to, e.g., human genes or gene products may have utility as potential drug compounds.

The invention discloses a method for constructing high-yield engineering bacteria of an oritavancin precursor cloireomycin. A high-yield chassis strain capable of being used for efficiently synthesizing glycopeptide antibiotics is constructed by knocking out an NRPS gene responsible for ristomycin biosynthesis in TNS106, inserting an integration site and then inserting a pJLL10 plasmid with a double-copy bbr gene. A bacterial artificial chromosome (BAC) plasmid containing a glycopeptide antibiotic biosynthetic gene cluster is introduced into the high-yield chassis strain to obtain the glycopeptide antibiotic high-yield engineering strain. The shake flask fermentation yield of the cloirusin high-producing strain obtained by the method disclosed by the invention can reach 1440mg / L, and the cloirusin high-producing strain is the strain with the highest shake flask fermentation yield in a public report.

Provided herein are engineered Streptomyces bacteria, and methods of using Streptomyces bacteria to produce Concanamycin A and Concanamycin B. The engineered Streptomyces bacteria overexpress one or more homologous regulator of the Concanamycin biosynthetic gene cluster (BGC), and express one or more heterologous regulator of the Concanamycin BGC. Further provided are optimized culture conditions for inducing Concanamycin A and Concanamycin B production, which can be used to culture Streptomyces bacteria or engineered Streptomyces bacteria.

Provided herein, inter alia, are compositions and methods for detecting guanitoxin producing bacteria in an aqueous liquid. The methods provided herein include detecting one or more more guanitoxin biosynthetic genes in the aqueous liquid. Compositions provided herein include one or more nucleic acids at least partially complementary to a guanitoxin biosynthetic gene.

This invention discloses a method for heterologous production of 7-aminodeacetoxycephalosporanic acid using *Aspergillus nidulans*. This invention targets a *Aspergillus nidulans* strain that heterologously produces 7-aminodeacetoxycephalosporanic acid. Genes derived from the biosynthetic gene clusters pcbAB / C, isopentine N-acetyltransferase gene, and cefE gene, or their mutants, are assembled into a *Aspergillus nidulans* expression vector. Co-expression is performed in a *Aspergillus nidulans* basal cell strain to obtain a recombinant strain, successfully achieving heterologous expression of 7-aminodeacetoxycephalosporanic acid in filamentous fungi. Experiments show that the yield can reach 0.13 g / L at the shake-flask level. The strain constructed in this invention provides a good heterologous expression system for studying the synthesis and regulatory mechanism of 7-aminodeacetoxycephalosporanic acid.

The invention discloses an insect-resistant and antibacterial pyrrole alkaloid compound and a biosynthetic gene cluster thereof. The structure of the pyrrole alkaloid compound is shown as a formula (I), wherein compounds 2, 3, 4, 14 and 15 are new compounds. The gene cluster of the pyrrole alkaloid compound is disclosed for the first time, and each gene function is confirmed for the first time. PasA and PasD act together to form a pyrrolidone skeleton intermediate 8, and then the compound 8 is converted into a final product 1 by PasB. The invention discloses the inhibitory activity of the compounds on chitinase, lepidoptera pests, namely plutella xylostella and agricultural pathogenic fungi, and a biosynthetic pathway of a lead compound 1 for the first time. The fatality rate of the compound 1 on lepidoptera pest plutella xylostella reaches 100%, the effect of the compound 1 is better than that of DFB, and the compound 1 also has good inhibition potential on agricultural pathogenic fungi. The invention provides a new alternative compound for pesticide development, and lays a solid foundation for realizing green and efficient synthesis of the compound 1.

The invention relates to the field of medicinal chemistry, and relates to a small molecule peptide for inhibiting growth of staphylococcus, and an analogue and application thereof. The method comprises the following steps: finding a rhodococcus genome from an NCBI (National Center of Biotechnology Information) microbial genome database, and predicting a non-ribosome peptide structure synthesized by a non-ribosome peptide synthetase (NRPS) sequence through software such as AntiSMASH and Prism; the method comprises the following steps: classifying all NRPS biosynthetic gene clusters (BGCs) through Bigscape to obtain a gene cluster family (GCFs); the method comprises the following steps: predicting the selectivity of a GCFs substrate and screening a polypeptide with antibacterial potential through Phammapper; a small molecule peptide (compound I) is obtained through chemical synthesis, and the small molecule peptide is found to have an inhibition effect on staphylococcus epidermidis and staphylococcus pseudointermedius; afterwards, alanine is used for replacing glutamine to increase hydrophobicity of glutamine (compound II), the antibacterial effect of the compound II is obviously enhanced, and the compound II has the potential of developing novel antibacterial drugs and biopesticides.

The invention discloses a biosynthetic gene cluster of polyether polydecalinmycin and an application of the biosynthetic gene cluster in construction of a high-yield strain. According to the invention, a biosynthetic gene cluster pdm of the polyether polydecalinmycin is positioned in a genome of streptomyces marincalensis SCSIO 03032, and a high-yield strain of the polydecalinmycin is successfully constructed by overexpressing a positive regulation gene pdmRI or pdmRII coded by the pdm gene cluster in a wild strain, so that the yield of the polydecalinmycin is increased by 48 times, and a material basis is provided for large-scale preparation, development and application of the polydecalinmycin.

The invention relates to a biosynthesis gene cluster of a tropolone compound, namely isatropolones, and a bacterial strain capable of realizing directional high yield. The gene cluster comprises an isaF gene, an isaJ gene and an isaS gene; the sequence of the isaF gene is as shown in SEQ ID NO.1, the sequence of the isaJ gene is as shown in SEQ ID NO.3, and the sequence of the isaS gene is as shown in SEQ ID NO.5. The strain capable of realizing the directional high yield is (1) a strain capable of realizing the directional high yield of isatropolone A, namely a strain which takes streptomyces sp.CGMCC (China General Microbiological Culture Collection Center) No.15540 as a host and is used for blocking an isaJ gene of the host or blocking an isaS gene of the host and is also used for realizing the overexpression of isaF at the same time, and the strain capable of realizing the directional high yield of the isatropolone A is a strain capable of realizing the directional high yield of the isatropolone A. And (2) the strain of the oriented high-yield isatropolone C is a strain which takes streptomyces sp.CGMCC (China General Microbiological Culture Collection Center) No.15540 as a host and is used for overexpressing the genes of isaF and isaS, or a strain which is used for overexpressing the genes of isaJ and isaS, or a strain which is used for overexpressing the genes of isaF, isaJ and isaS, or a strain which is used for overexpressing the genes of isaF, isaJ and isaS.

The invention provides a tandem gene for biosynthesizing astaxanthin in rape seeds, an expression cassette and an expression method, and belongs to the technical field of gene engineering. The invention provides a tandem gene for biosynthesis of astaxanthin, and four carotenoid anabolism genes are firstly constructed into the tandem gene for a biosynthesis path of astaxanthin. The four carotenoid anabolism genes are driven based on the rape seed specific NAPIN promoter to construct an astaxanthin biosynthesis path in the rape seeds and synthesize the astaxanthin, so that the biosynthesis efficiency of the astaxanthin is improved; the expression of the astaxanthin biosynthetic gene and the accumulation of the astaxanthin in the seeds do not influence the growth, development and reproduction of the rape; in addition, fat-soluble carotenoid and astaxanthin are naturally integrated with grease in the rape seeds, and astaxanthin rapeseed oil is directly used as a product, so that the activity of astaxanthin is maintained, and the later astaxanthin extraction production cost can be reduced.

The invention relates to an engineering bacterium for producing UK-2A and application of the engineering bacterium. The UK-2A biosynthetic gene cluster is reconstructed by adding a promoter in front of a ukaA gene of the UK-2A biosynthetic gene cluster, adding a promoter rpsLp-cf in front of a ukaB gene and adding a promoter SP23 in front of a ukaC gene, an expression vector containing the reconstructed UK-2A gene cluster is constructed and introduced into streptomyces albus J1074, UK-2A is efficiently produced by using a better fermentation culture medium, and the UK-2A biosynthetic gene cluster has the advantages that the UK-2A biosynthetic gene cluster is high in yield; the shake-flask fermentation yield of the engineering bacteria reaches 1500 micrograms / mL or above, and compared with the engineering bacteria of the UK-2A gene cluster before reconstruction, the UK-2A yield is greatly improved.