21 results about "Nonribosomal peptide" patented technology

This application relates to the field of biosynthesis technology, and specifically discloses a pyridone compound, its biosynthesis method and application. Based on synthetic biology-related technologies, this application modifies non-ribosomal peptide synthetase, heterologously expresses non-ribosomal peptide synthetase mutants in a variety of hosts, and for the first time discovers and obtains a pyridone compound, and determines its chemical formula as C5H4N2O3, named 5-amino-pyridine-2,3,6-trione or 5-hydroxy-3-imino-pyridine-2,6-dione. This novel pyridone compound can be used as a raw material or intermediate in the development and preparation of novel antibiotics, drugs and dyes.

The invention discloses a combined module for improving the yield of actinomycetes polyketone natural products and construction and application of recombinant bacteria containing the combined module, and belongs to the technical field of genetic engineering. In order to improve the yield of natural products such as polyketone, non-ribosome peptide and the like, the invention provides a combined module capable of improving the yield of actinomycetes natural products by combining and transforming a synthesis pathway of CoASH and a post-modification pathway of PPTase through a metabolic engineering strategy, and the module consists of CoASH cofactor synthesis module elements SCoaAR106A and SCoaD and a PPTase post-modification module element HPC3. By constructing a recombinant vector and recombinant bacteria containing the combined module, the yield of natural products such as actinomycetes polyketone, polyether and non-ribosomal peptide can be effectively improved by over-expression of the combined module.

This invention relates to a combined module for increasing the yield of polyketide natural products from actinomycetes, and the construction and application of recombinant bacteria containing this module, belonging to the field of genetic engineering technology. To improve the yield of natural products such as polyketides and nonribosomal peptides, this invention utilizes a metabolic engineering strategy to combine and modify the CoASH synthetic pathway and the PPTase post-modification pathway, providing a combined module that can increase the yield of natural products from actinomycetes. This module consists of the CoASH cofactor synthesis module element SCoaA. R106A Composed of SCoaD and PPTase post-modification module element HPC3, recombinant vectors and recombinant bacteria containing this module were constructed. It was found that overexpression of this module can effectively increase the yield of natural products such as actinomycete polyketides, polyethers, and non-ribosomal peptides.

The present invention relates to the application of phosphopantetheinyltransferase E7X1, its encoding gene, recombinant vectors containing the gene, and recombinant bacteria, belonging to the field of genetic engineering technology. To increase the yield of natural products such as polyketides and non-ribosomal peptides, the present invention utilizes bioinformatics analysis and other means to mine a highly efficient phosphopantetheinyltransferase E7X1 from a database. The amino acid sequence of the enzyme is shown in SEQ ID NO.1, and the nucleotide sequence of the gene encoding the enzyme is shown in SEQ ID NO.2. By constructing a recombinant vector and recombinant bacteria containing the enzyme encoding gene, the present invention discovered that overexpressing the enzyme can effectively increase the yield of natural products such as polyketides, polyethers, and non-ribosomal peptides.

The present invention relates to the application of phosphopantetheinyltransferase A5L6, its encoding gene, recombinant vectors containing the gene, and recombinant bacteria, belonging to the field of genetic engineering technology. To increase the yield of natural products such as polyketides and non-ribosomal peptides, the present invention utilizes bioinformatics analysis and other means to mine a highly efficient phosphopantetheinyltransferase A5L6 from a database. The amino acid sequence of the enzyme is shown in SEQ ID NO.1, and the nucleotide sequence of the gene encoding the enzyme is shown in SEQ ID NO.2. By constructing a recombinant vector and recombinant bacteria containing the enzyme encoding gene, the present invention discovered that overexpressing the enzyme can effectively increase the yield of natural products such as polyketides, polyethers, and non-ribosomal peptides.

The present invention discloses a strain of Pseudomonas and a preparation method and application of the non-ribosomal peptide produced thereby. The Pseudomonas HN8-3 of the present invention is isolated from the rhizosphere soil of Lens culinaris in Gansu Province and can produce pseudophomins A-D through liquid fermentation. These substances can be separated and purified into monomeric compounds by solid-phase extraction technology combined with high-performance liquid chromatography technology. Under in vitro experimental conditions, pseudophomins A-D at a concentration of 1 μM can well lyse the zoospores of Phytophthora capsici ( Phytophthora capsici ). On the living body of plants (cucumber leaves), the compounds at a concentration of 10 μM can well prevent and control the occurrence of diseases caused by Phytophthora capsici. Compared with the control group, this concentration can achieve a 100% effect in preventing and controlling Phytophthora capsici. Thus, it can be seen that pseudophomins A-D have a good effect in preventing and controlling Phytophthora capsici. Such lead compounds have the potential to be used as biological agents and biological drugs and can be used as the parent compounds of Pseudomonas-derived biological pesticides, having important potential application values in the fields of agricultural production and the like.

The present invention provides a chimeric polyketide synthase (PKS) or polyketide synthase-nonribosomal peptide synthetase (PKS-NRPS) and uses thereof, wherein the PKS or PKS-NRPS comprises two or more recombinant units (RUs) linked to each other, wherein each RU comprises one or two or more contiguous domains derived from a parent PKS or PKS-NRPS, and the junction of at least one RU is defined by a recombination site selected from a site at the LPTY (A / P) FQ (H / R) xRYWL motif located in the AT post- linker (RYWL motif site) and a site at the RL motif of ACP helix 0 (RL motif site); wherein the two or more RUs are not naturally linked to each other.

The present invention relates to the application of phosphopantetheinyltransferase AU23, its encoding gene, recombinant vectors containing the gene, and recombinant bacteria, which belong to the field of genetic engineering technology. To increase the yield of natural products such as polyketides and non-ribosomal peptides, the present invention uses bioinformatics analysis and other means to mine a highly efficient phosphopantetheinyltransferase AU23 from a database. The amino acid sequence of the enzyme is shown in SEQ ID NO.1, and the nucleotide sequence of the gene encoding the enzyme is shown in SEQ ID NO.2. By constructing a recombinant vector and recombinant bacteria containing the enzyme encoding gene, the present invention found that overexpressing the enzyme can effectively increase the yield of natural products such as polyketides, polyethers, and non-ribosomal peptides.

The present disclosure pertains to produce a novel NRPS. In the present disclosure, a restriction enzyme recognition sequence was successfully introduced into a nucleic acid encoding an NRPS while maintaining a function of producing a target NRP. Various NRPSs can be produced using the introduced restriction enzyme recognition sequence. In one aspect, the present disclosure provides a nucleic acid containing a non-native restriction enzyme recognition sequence and encoding an NRPS. In another aspect, the present disclosure provides a method for efficiently producing a nucleic acid encoding a novel NRPS using a non-native restriction enzyme recognition sequence. In addition, the present disclosure also provides a novel NRPS and a novel NRP.

This invention discloses a strain of *Bacillus belyceae* with broad-spectrum antibacterial activity and its application in the prevention and treatment of necrotic enteritis in poultry. The *Bacillus belyceae* strain provided by this invention (… Bacillus from Velez The genome of strain GDG25CB056 is approximately 3.91 Mb in size, contains no virulence factors, and is rich in gene clusters encoding non-ribosomal peptides and polyketide synthases. Studies have confirmed that this strain exhibits significant growth advantages, strong tolerance to high temperatures, gastric acid, and bile salts, which facilitates intestinal colonization. It can produce siderophores and various enzymes, and has overcome the technical bottleneck of a narrow antibacterial spectrum, possessing broad-spectrum antibacterial activity, especially strong specific antagonistic activity against Clostridium perfringens. In vivo experiments have shown that this strain can significantly reduce the Clostridium perfringens load in the cecum of chicks with necrotizing enterocolitis, alleviate intestinal congestion and swelling, repair damaged intestinal villi, and enhance mucosal barrier function, providing a safe and efficient strain resource for the prevention and treatment of bacterial enteric diseases.

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 double-target antibacterial lipopeptide and a preparation method thereof, and relates to the technical field of biology, the lipopeptide can be combined with double targets on Gram-positive bacteria or Gram-negative bacteria, and the lipopeptide can be synthesized according to a non-ribosome peptide synthesis rule on the basis of a non-ribosome peptide synthesis gene coded by aquimarina sp.EL43. The method comprises the following steps of: directly predicting a substrate (amino acid or organic acid and the like) recognized by the adenylation structural domain enzyme activity central site by using the composition of 10 conservative position amino acids at the adenylation structural domain enzyme activity central site, deducing a linear polypeptide sequence coded by a gene cluster, and then adding myristic acid fatty acid side chains widely used by lipopeptides, and adopting a polypeptide solid-phase synthesis strategy. The invention provides the novel antibiotic which is safe, effective, not easy to generate drug resistance and relatively low in cost, and the preparation method thereof.

The present invention relates to the application of phosphopantetheinyltransferase B3D0, its encoding gene, recombinant vectors containing the gene, and recombinant bacteria, belonging to the field of genetic engineering technology. To increase the yield of natural products such as polyketides and non-ribosomal peptides, the present invention utilizes bioinformatics analysis and other means to mine a highly efficient phosphopantetheinyltransferase B3D0 from a database. The amino acid sequence of the enzyme is shown in SEQ ID NO.1, and the nucleotide sequence of the gene encoding the enzyme is shown in SEQ ID NO.2. By constructing a recombinant vector and recombinant bacteria containing the enzyme encoding gene, the present invention discovered that overexpressing the enzyme can effectively increase the yield of natural products such as polyketides, polyethers, and non-ribosomal peptides.

The application discloses an amino acid sequence of tranexamic acid-carnosine ligase, and a preparation method of tranexamic acid-carnosine conjugate. The amino acid sequence of the tranexamic acid-carnosine ligase is shown as SEQ ID NO: 4. The tranexamic acid-carnosine ligase is fused by an adenylation (A) domain, a thioesterification (T) domain and a condensation (C) domain. The adenylation domain is obtained by mutation and modification of an adenylation domain in non-ribosomal peptide synthetase from Streptomyces coelicolor. After the mutation and modification, the adenylation domain has high specificity for a substrate tranexamic acid, can efficiently recognize and activate the tranexamic acid, so that the tranexamic acid-carnosine ligase can efficiently catalyze the reaction of the tranexamic acid and L-carnosine to generate the tranexamic acid-carnosine conjugate.

Disclosed herein are recombinant methods of activating expression of one or more biosynthetic gene clusters comprising more than one gene, the method comprising a recombinant DNA expression vector that possess two opposable inducible promoters that drives expression of a biosynthetic gene cluster exogenously from outside of the cluster to produce polyketides or non-ribosomal peptides in a heterologous host.

The present invention relates to the field of medicinal chemistry and relates to a small molecule peptide with anti-cancer activity and its application. By analyzing the non-ribosomal peptide synthetase (NRPS) sequence of a Rhodococcus erythropolis strain using bioinformatics software, the possible molecular backbone of the non-ribosomal peptide synthesized by this NRPS was predicted, and a series of small molecule peptides were obtained through chemical synthesis. After activity testing, one of the small molecule peptides was screened out to have a relatively obvious inhibitory effect on the cancer cell line HT29, and it has the value for the development of new anti-cancer drugs.

The present invention provides a composition comprising a biologically pure culture of a Paenibacillus sp. strain or a cell-free preparation thereof comprising a fusaricidin and a tridecaptin; wherein the fusaricidin is produced with a fusaricidin synthetase gene of fusA encoded by a DNA sequence exhibiting at least 90.5% sequence identity to SEQ ID NO: 3; and the tridecaptin is produced with a nonribosomal peptide synthetase (NRPS) gene of triE encoded by a DNA sequence exhibiting at least 90.0% sequence identity to SEQ ID NO: 7. Also provided are methods of treating an agricultural plant to control a disease and methods of increasing the vigor and / or crop yield of an agricultural plant with the disclosed compositions.

The present invention relates to the application of phosphopantetheinyltransferase ZF92, its encoding gene, recombinant vectors containing the gene, and recombinant bacteria, belonging to the field of genetic engineering technology. To increase the yield of natural products such as polyketides and non-ribosomal peptides, the present invention utilizes bioinformatics analysis and other means to mine a highly efficient phosphopantetheinyltransferase ZF92 from a database. The amino acid sequence of the enzyme is shown in SEQ ID NO.1, and the nucleotide sequence of the gene encoding the enzyme is shown in SEQ ID NO.2. By constructing a recombinant vector and recombinant bacteria containing the enzyme encoding gene, the present invention discovered that overexpressing the enzyme can effectively increase the yield of natural products such as polyketides, polyethers, and non-ribosomal peptides.

The present invention provides a chimeric polyketide synthase (PKS) or polyketide synthase-non-ribosomal peptide synthetase (PKS-NRPS) and the use thereof, wherein the PKS or PKS-NRPS comprises two or more recombination units (RU) which are joined to each other, wherein each RU comprises one or two or more contiguous domains derived from a parental PKS or PKS-NRPS and the junction end of at least one RU is defined by a recombination site selected from a site at the LPTY (A / P) FQ (H / R) xRYWL motif at post AT-linker (the RYWL motif site) and a site at the RL motif at ACP helix 0 (the RL motif site); wherein the two or more RUs are not naturally joined with each other.

The present invention provides a genetically modified host cell capable of producing Porphyra-334 and / or Shinorine, which comprises (a) (i) a 2-demethyl-4-deoxycod's alcohol synthase (DDGS), (ii) an O-methyltransferase (O-MT or OMT), (iii) an ATP dependent carboxylic acid-amine ligase, and (iv) a non-ribosomal peptide synthetase (NRPS) or a D-ala-D-ala ligase, MysD or MysE; or (b) MysA, MysB, MysC or MysD, MysE or NRPS; wherein one or more of the foregoing enzymes are their homologous enzymes.

The application belongs to the technical field of medical compounds, and particularly relates to an anti-tumor polyketide-nonribosomal peptide hybrid compound, a preparation method and application. The polyketide-nonribosomal peptide hybrid compound is compound 1 or compound 2, and structural formulas of the compound 1 and the compound 2 are as follows: The compound has anti-tumor activity, particularly anti-human breast cancer effect, and has relatively high anti-tumor activity.