755results about "Ligases" patented technology

The invention discloses a novel application of an RNF6 gene, namely, an application of screening a medicine for preventing and / or treating Zika virus infection, aiming at inhibiting expression of the RNF6 gene or knocking out the RNF6 gene. A series of functional experiments prove that the RNF6 gene promotes the replication of the Zika virus, and the purpose of reducing the replication of the Zika virus can be achieved by using an expression inhibitor of the RNF6 gene or knocking out the RNF6 gene; experimental results show that the RNF6 gene can be used as a potential target for preventing and / or treating Zika virus infection, and a new direction is provided for development of drugs for preventing and / or treating Zika virus infection targeting the RNF6 gene in the future.

Described herein are programmable DNA proteolytic target chimera complexes that can be used both for the direct treatment of cancer by inhibiting biochemical pathways that are overexpressed in cancer cells, and for the indirect treatment of cancer by recruiting the E3 ligase complex to engage with a protein of interest or a mutant thereof and initiating proteolysis. Also described herein are methods of using the complexes in the treatment of cancer, as well as compositions comprising the complexes.

The disclosure provides, for example, double stranded DNA (dsDNA) molecules comprising one or more chemically modified nucleobases. In some embodiments, the dsDNA molecule is circular and comprises a first strand and a second strand, wherein the first strand comprises one or more chemically modified nucleobases, and the second strand is free of chemically modified nucleobases. In some embodiments, the dsDNA molecule comprises a promoter sequence and an effector sequence that encodes an effector.

The invention belongs to the field of biosynthesis, and in particular relates to LBD (Levandanenediol Pyrophosphate) synthase and engineered yeast for producing sclareol. In order to solve the problem that in the prior art, the sclareol biosynthesis yield is generally low, LSLPPs mutant containing at least one mutation of D730L, D374L, N674L or G379M is obtained by performing mutation and optimization on LSLPPs pyrophosphate synthase, and the mutant is used for sclareol synthesis. Meanwhile, in order to solve the problem of genetic instability caused by free plasmid expression of part of saccharomyces cerevisiae strains, a sclareol synthesis pathway is constructed in a yeast genome, and meanwhile, an acetyl coenzyme A synthesis pathway, an MVA pathway and a sclareol synthesis pathway are enhanced; chassis bacteria for synthesizing sclareol are modified in a manner of knocking out part of transcription inhibition factors, and the yield of a 5L fermentation tank reaches 26.11 g / L and is greatly improved compared with the prior art.

Disclosed herein are methods of increasing nitrogen fixation in a non-leguminous plant. The methods can comprise exposing the plant to a plurality of bacteria. Each member of the plurality comprises one or more genetic variations introduced into one or more genes or non-coding polynucleotides of the bacteria's nitrogen fixation or assimilation genetic regulatory network, such that the bacteria are capable of fixing atmospheric nitrogen in the presence of exogenous nitrogen. The bacteria are not intergeneric microorganisms. Additionally, the bacteria, in planta, produce 1% or more of the fixed nitrogen in the plant.

The application relates to an engineering bacterium for high yield of observation blue and a construction method and application thereof, and belongs to the technical field of biological synthesis of natural dyes. The engineering bacterium for high yield of observation blue expresses icd, bpsA, glnA Y405F and gdhA; the engineering bacterium knocks out acnR, yggB, glsK, aceA and ldh. By knocking out the yggB and aceA genes, performing site-directed mutation (Y405F) on the glnA gene, replacing the glsK gene with the glnA Y405F gene, replacing the acnR gene with the icd gene, replacing the ldh gene with the gdhA gene, and integrating the bpsA gene, the application can block the formation of by-products such as lactate and succinic acid in the observation blue synthesis process, improve the flow direction of the citric acid->isocitric acid->alpha-ketoglutaric acid->glutamic acid->glutamine path, and then improve the intracellular glutamine concentration, so that the yield of observation blue is improved.

The invention belongs to the field of biosynthesis, and particularly relates to sclareol synthase and engineered yeast for producing sclareol. In order to solve the problem that in the prior art, sclareol biosynthesis yield is generally low, sclareol synthase is mutated and optimized, an SsScs mutant containing at least one mutation of Y491F, G307L or N269F is obtained, and the mutant is used for sclareol synthesis. Meanwhile, in order to solve the problem of genetic instability caused by free plasmid expression of part of saccharomyces cerevisiae strains, a sclareol synthesis pathway is constructed in a yeast genome, and meanwhile, an acetyl coenzyme A synthesis pathway, an MVA pathway and a sclareol synthesis pathway are enhanced; chassis bacteria for synthesizing sclareol are modified in a manner of knocking out part of transcription inhibition factors, and the yield of a 5L fermentation tank reaches 21.13 g / L and is greatly improved compared with the prior art.

The invention belongs to the field of plant seed biology and rice breeding, and discloses an application of an OsBTB05 gene or an OsBTB05 protein in regulation and control of storage resistance of rice seeds and a related breeding method. In particular discloses application of an OsBTB05 gene or an OsBTB05 protein in regulation and control of the storability of rice seeds, the nucleotide sequence of the OsBTB05 gene is shown as SEQ ID NO: 1 or SEQ ID NO: 2, and the amino acid sequence of the OsBTB05 protein is shown as SEQ ID NO: 3. The invention also discloses a molecular marker-assisted selection method for breeding the high-storage-resistance rice variety and a method for reducing the storage resistance of the rice seeds. The invention proves that the OsBTB05 gene is a key factor for regulating and controlling the storability of the rice seeds, and the expression level of the OsBTB05 gene is in significant positive correlation with the storability of the seeds. A clear molecular target and a brand-new gene resource are provided for improving the seed storage resistance from a genetic source.

The invention discloses a glutathione bifunctional synthetase mutant with improved catalytic activity and application, and belongs to the field of gene engineering and fermentation engineering. A series of mutants with improved enzyme activity are obtained by carrying out site-specific combinatorial mutation on a site 61, a site 136, a site 485, a site 498 and a site 722 of the glutathione bifunctional synthetase GshFst, the specific enzyme activity reaches 13.58 U.mg <-1 >-27.34 U.mg <-1 >, the half-life period at 37 DEG C reaches 195-320 min, and the enzyme activity and the thermal stability are remarkably improved compared with those of a wild type. The enzyme mutant provided by the invention has a wide application prospect in the production of glutathione and the construction of genetically engineered microorganisms for producing glutathione.

The present disclosure provides guided microbial remodeling (GMR) methods for the rational improvement of plant-associated microbes to perform plant-beneficial functions. The GMR methods described herein allow for non-intergeneric genetic optimization of key regulatory networks within the microbes, which improve plant-beneficial functions over wild-type microbes but don't have the risks associated with transgenic approaches (e.g., unpredictable gene function, public and regulatory concerns, etc.). The present disclosure also provides remodeled microbes and compositions thereof. The utilization of remodeled microbes and compositions thereof will enable farmers to realize more productive and predictable crop yields without the nutrient degradation, leaching, or toxic runoff associated with traditional synthetically derived fertilizers.

The invention relates to the technical field of synthetic biology and microbial engineering, in particular to recombinant escherichia coli for de novo synthesis of forsythiaside A. The invention provides recombinant escherichia coli for de novo synthesis of forsythiaside A. A preparation method of the recombinant escherichia coli comprises a step of improving an escherichia coli starting strain, and the escherichia coli starting strain is escherichia coli MG1655. In the fermentation process of the recombinant escherichia coli, effective accumulation of forsythiaside A in fermentation liquor can be achieved, and a foundation can be laid for subsequent construction of high-yield forsythiaside A engineering bacteria.

Genetically engineered immune cells, which express at least two metabolism modulating polypeptides and optionally a chimeric receptor polypeptide (e.g., an antibody-coupled T cell receptor (ACTR) polypeptide or a chimeric antigen receptor (CAR) polypeptide) capable of binding to a target antigen of interest. Also disclosed herein are uses of the engineered immune cells for inhibiting cells expressing a target antigen in a subject in need thereof.

The invention provides a resveratrol production strain and a construction method and application thereof, according to the strain, tyrAfbr, tyrB, aroE, pntAB, ompF, aroGfbr and accA genes are up-regulated, a carbon storage regulation factor csrA gene is knocked out, the transcriptional level of a fabF gene is down-regulated through a BBaJ23113 promoter, a TAL gene from Rhodotorula glutinis, a 4CL gene from Arabidopsis thaliana and an STS gene from Vitis vinifera are heterologously expressed on a genome, and the strain carries a high-copy plasmid PET-28a-WAL at the same time; the strain takes glucose as a carbon source, resveratrol is efficiently and stably synthesized from the beginning by adopting a fermentation method, the production cost is low, and efficient production of resveratrol is realized.

The invention discloses engineered saccharomyces cerevisiae and application of the engineered saccharomyces cerevisiae in synthesis of 2-phenethyl alcohol, and belongs to the technical field of genetic engineering. According to the engineering saccharomyces cerevisiae, saccharomyces cerevisiae CICC 33068 is modified, and the strain is modified through strategies such as aldrin pathway enhancement, precursor enhancement, tolerance optimization and cofactor balance. The constructed engineered strain has good metabolic performance and stability, not only is the tolerance of the engineered strain to 2-phenethyl alcohol improved, but also the production capacity of the 2-phenethyl alcohol is remarkably improved. Therefore, the engineered saccharomyces cerevisiae disclosed by the invention has remarkable advantages in production of the 2-phenethyl alcohol, can provide technical guidance for industrial production of the 2-phenethyl alcohol, and has a good application prospect.

The invention relates to a strong promoter P7 suitable for streptomyces and application thereof, and relates to the field of genetic engineering and microbial metabolism engineering. The nucleotide sequence of the strong promoter P7 is as shown in SEQ ID No.1, and the strong promoter comprises a plasmid vector of the strong promoter; a host cell comprising the plasmid vector; the invention also discloses application of the strong promoter, the plasmid vector and the host cell in starting expression of a target gene. Compared with the prior art, the characterization of the strong promoter P7 provides an effective tool element for streptomyces strong promoter engineering and high-efficiency gene expression, and has important significance on streptomyces silent gene characterization, high-efficiency gene expression, metabolite synthesis, metabolic pathway reconstruction and the like. The strong promoter can be applied to common streptomyces type strains, and has important significance on high yield of important proteins including enzymes and important metabolites from actinomycetes.

The invention relates to the field of plant genetic engineering. Specifically, the invention relates to a method for creating a novel herbicide-resistant plant through a plant basic group editing technology and screening an endogenous gene mutation site capable of endowing the plant with herbicide resistance. The invention also relates to the use of the identified mutated endogenous resistance gene in crop breeding.

The invention discloses pichia kudriavzevii for high yield of L-malic acid as well as a construction method and application thereof, and belongs to the technical field of biology, the pichia kudriavzevii is named as YM-023 and classified as Pichia kudriavzevii, the preservation number is CGMCC No. 35487, the preservation time is July 31, 2025, and the preservation number is CGMCC No. 35487. The preservation unit is China General Microbiological Culture Collection Center (CGMCC). The method comprises the following steps: starting from an acid-resistant yeast Kudriavzevii pichia pastoris strain YL-000 (the preservation number is CGMCC No.35680), carrying out metabolic engineering transformation to obtain a transformed strain, and ensuring that the transformed strain can realize efficient production of L-malic acid in a fermentation mode of adding a small amount of calcium carbonate neutralizer.

The present disclosure provides a recombinant Escherichia coli strain modified by metabolic engineering means and a method for producing L-homoserine by using the same. The strain, designated as Escherichia coli having a strain number of 13-XA, is deposited in China General Microbiological Culture Collection Center (CGMCC) with an accession number of CGMCC No. 25099, dated Jun. 16, 2022. With respect to the chromosome DNA thereof, one or more genes associated with fatty acid metabolism are knocked out or attenuated, and / or a promoter is replaced for enhancement; one or more genes associated with the L-homoserine metabolic pathway are knocked out or attenuated, and / or one or more genes associated with the L-homoserine metabolic pathway are overexpressed or enhanced, and / or one or more genes associated with the L-homoserine metabolic pathway are mutated.

The disclosure provides, for example, double stranded DNA (dsDNA) molecules comprising one or more chemically modified nucleobases. In some embodiments, the dsDNA molecule is circular and comprises a first strand and a second strand, wherein the first strand comprises one or more chemically modified nucleobases, and the second strand is free of chemically modified nucleobases. In some embodiments, the dsDNA molecule comprises a promoter sequence and an effector sequence that encodes an effector.

This invention specifically relates to a de novo 7-DHC-synthesizing *Saccharomyces cerevisiae* genetically engineered strain, its construction method, and its applications, belonging to the field of biotechnology. Using *Saccharomyces cerevisiae* engineered strain SC9 as the starting strain, this invention utilizes multiple copies of tHMG1, DHCR24, and ERG1 via the TY transposon, multiple copies of ERG2, POS5, ERG7, ERG11, IDI1, and ERG3 via the TY transposon, and single copies of POS5, ERG3, and DHCR24 in the genome to increase the intracellular content of reducing coenzyme II and enhance the main pathway of 7-DHC synthesis. Single copies of ACL, ACS1, ERG10, and ERG19 in the genome enhance the utilization of ethanol in *Saccharomyces cerevisiae* and dynamically regulate the synthesis of 7-DHC. The *Saccharomyces cerevisiae* genetically engineered strain constructed by this invention exhibits high product accumulation, laying the foundation for replacing traditional multi-step chemical synthesis routes and realizing industrial production.

The invention discloses yarrowia lipolytica with high yield of beta-carotene as well as a construction method and application of the yarrowia lipolytica. According to the yarrowia lipolytica engineering bacterium, geranyl diphosphate synthase gene xdGPS, phytoene dehydrogenase gene CarB, phytoene cyclization / phytoene synthesis bifunctional enzyme mutant gene GarRPY27R, acetyl-coenzyme A synthetase mutant gene ACSL641P and pyruvate ferredoxin oxidoreductase gene nifJ are integrated and expressed on a chromosome, and the yarrowia lipolytica engineering bacterium is obtained. Meanwhile, a 3-hydroxy-3-methylglutaryl CoA reductase gene HMGR (3-hydroxy-3-methylglutaryl CoA reductase) derived from the yarrowia lipolytica strain is subjected to overexpression; the yield of the beta-carotene is increased to 13.186 g / L, and the production efficiency is 0.14 g / L / h.

This present disclosure provides adeno-associated viral vectors, recombinant adeno-associated virus (rAAV), and methods of their use in gene therapy for treating propionic acidemia (PA). Also provided are pharmaceutical compositions comprising a recombinant adeno-associated virus of the invention and a pharmaceutically acceptable carrier or excipient. These pharmaceutical compositions may be useful in gene therapy for the treatment of PA caused by mutations in propionyl-CoA carboxylase α-subunit (PCCA) or mutations in propionyl-CoA carboxylase β-subunit (PCCB).

The invention belongs to the technical field of bioengineering, and discloses a genetic engineering strain for enhancing schizochytrium limacinum DHA oil production based on carbon flux guidance and fatty acid transport, a method and application thereof. The gene engineering strain is obtained by introducing an optimized coding gene ACLY and / or Fat1p coding gene related to guiding carbon flux and fatty acid transport into a schizochytrium limacinum body; wherein the gene sequence of the gene ACLY is SEQ ID No. 9, and the gene sequence of the gene Fat1p is SEQ ID No. 10. According to the invention, a schizochytrium limacinum engineering bacterium for enhancing DHA oil production based on carbon flux guidance and fatty acid transfer is constructed by means of metabolic engineering. The schizochytrium limacinum engineering bacterium is combined with fatty acid transfer based on carbon flux guiding, can be used for grease synthesis by guiding carbon flux, and can prevent grease from being degraded through fatty acid transfer.

This present disclosure provides adeno-associated viral vectors, recombinant adeno-associated virus (rAAV), and methods of their use in gene therapy for treating propionic acidemia (PA). Also provided are pharmaceutical compositions comprising a recombinant adeno-associated virus of the invention and a pharmaceutically acceptable carrier or excipient. These pharmaceutical (compositions may be useful in gene therapy for the treatment of PA caused by mutations in propionyl-CoA carboxylase α-subunit (PCCA) or mutations in propionyl-CoA carboxylase β-subunit (PCCB).

The invention provides an L-lysine production strain as well as a strain construction method and application. A hom (V59A) is introduced on a genome by utilizing a homologous recombination gene editing technology to weaken a competitive approach of lysine; the lysC (T311I) which is not inhibited by L-lysine is overexpressed; the method comprises the following steps of: overexpressing lysE, lysA, ddh, dapB and asd, knocking out a lysI gene and multi-copying the lysE, carrying out synchronous multi-copying on the dapA and EcdapB genes through a manual operon P1676-EcdapB-Pa12-dapA, and carrying out synchronous multi-copying on the dapB, ddh, lysA and lysO genes through a manual operon Psod-dapB-ddh-Ptuf-lysO-lysA; the constructed strain does not contain plasmids, has no defects, does not need induction, has the advantages of good genetic stability, high fermentation yield and the like, and can be used for stably producing L-lysine.

A recombinant microbial cell is capable of producing at least one compound having structural Formula II from a carbon source:In Formula II, n=2-3; R1=H or COCH3 or CH2CH2COX with X=OH or O—; R2=CH3 or CH2CH2COX with X=OH or O— where the cell comprises a genetic modification to increase activity relative to its wild-type cell of E4 where E4 is a desferrioxamine or bisucaberin synthetase (EC 6.3.-.-) (E4i) capable of converting N5-aminopentyl-N-(hydroxy)-succinamic acid to desferrioxamine B or H or at least one other linear desferrioxamine or bisucaberin according to Formula II.

Provided herein are compositions and methods for cross-linking multi-specific antibodies to targets with conjugates. Further provided herein are conjugates comprising targeting domains, wherein the targeting domain comprises an unnatural amino acid. Further provided herein are methods of treating disease with cross-linking multi-specific antibodies.

The present invention relates to a novel CRS fragment peptide having immune enhancing activity and its use, more specifically, to a novel peptide consisting of the amino acid sequence of SEQ ID NO: 2 and its use as a vaccine adjuvant and a cancer therapeutic agent. The peptide disclosed in the present invention exhibits anti-cancer activity and immune function enhancing activity as the CRS fragment disclosed for the first time in the present specification.

The invention belongs to the technical field of biology, and particularly relates to a fusion protein and application thereof in competitive inhibition of MDM2 and further recovery of TP53 activity. The fusion protein provided by the invention comprises an antibody fragment, a modified progesterone receptor and an RING subunit of an antibody receptor Trim21 which are connected in sequence, has a composite structure of an antibody and a part of subunits of the Trim21, can specifically degrade a target protein, competitively inhibits MDM2 while degrading the target protein, further recovers the activity of a P53 gene, and has a good application prospect. The anti-tumor effect is also realized.

A composition for use in treatment or prevention of a TAR DNA-binding protein 43 related disease, comprising a promoting substance that increases an intracellular amount of a protein having ubiquitination activity.