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36 results about "Streptomyces roseosporus" patented technology
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Streptomyces roseosporus is a species of actinobacteria. It produces the novel cyclic lipopeptide antibiotic daptomycin (US trade name: Cubicin).
High Purity Lipopeptides
The invention discloses highly purified daptomycin and to pharmaceutical compositions comprising this compound. The invention discloses a method of purifying daptomycin comprising the sequential steps of anion exchange chromatography, hydrophobic interaction chromatography and anion exchange chromatography. The invention also discloses a method of purifying daptomycin by modified buffer enhanced anion exchange chromatography. The invention also discloses an improved method for producing daptomycin by fermentation of Streptomyces roseosporus. The invention also discloses high pressure liquid chromatography methods for analysis of daptomycin purity. The invention also discloses lipopeptide micelles and methods of making the micelles. The invention also discloses methods of using lipopeptide micelles for purifying lipopeptide antibiotics, such as daptomycin. The invention also discloses using lipopeptide micelles therapeutically.
Owner:CUBIST PHARMA INC
Screening method for breeding Streptomyces roseosporus strains producing Daptomycin and obtained strains
InactiveCN101892287AImprove screening efficiencyReduce manufacturing costBacteriaMicrobiological testing/measurementStreptomycesWild type
The invention discloses a screening method for breeding Streptomyces roseosporus strains producing Daptomycin and the obtained strains. The screening method comprises the following steps of: 1) coating bacteria liquid of wild Streptomyces roseosporus or mutant strains thereof subjected to mutagenesis on a solid panel containing streptomycin and / or Daptomycin, and culturing to obtain streptomycin and / or Daptomycin tolerant Streptomyces roseosporus; and 2) respectively selecting a single colony of the streptomycin and / or Daptomycin tolerant Streptomyces roseosporus for shake flask fermentation, detecting the Daptomycin content in fermented materials, and selecting strains with the Daptomycin content higher than that of starting strains. The screening method has the advantages of directivity, intuition, simpleness, quickness, high efficiency, great reduction of workload, and acceleration of strain breeding process. The Daptomycin fermentation unit of the screened Streptomyces roseosporus strains is obviously improved, which can be improved by more than 5 times to the maximum.
Owner:SHANGHAI INST OF PHARMA IND
Batch type feed-batch fermentation method for streptomyces roseosporus to produce Daptomycin efficiently
ActiveCN101824452AIncrease productionControllable fermentation processMicroorganism based processesFermentationSporeStreptomyces
The invention relates to a batch type feed-batch fermentation method for streptomyces roseosporus to produce Daptomycin efficiently, comprising the following steps: taking streptomyces roseosporus slant spore at normal temperature to prepare spore suspension by sterile water; inoculating 0.5ml of the spore suspension in a 250ml shake flask filled with 30ml of seed culture medium, and culturing for 48h in a shaker when the temperature is 28-32 DEG C and the revolution speed is 180-220 rpm; adding 1% of inoculum size in an automatic 7.5 LDE fermentation tank loaded with fermentation medium; adding one or combination of cofactor ferroheme or leucovorin or pyridoxal phosphate VB6 with the concentration of 0.5-30mg / L; and controlling the throughput to be 0.8-1.2v / v / m, the pH value to be 6.5-7.5 and fermenting for 90-144h at the temperature of 28-32 DEG C. By adopting the method in the invention to regulate biological enzyme activity to increase intracellular metabolism flux introduced in Daptomycin synthesis, the Daptomycin yield is improved; the method has simple operation and low cost; and in the streptomyces roseosporus fermented and cultured by the invention, the fermentation unit of the Daptomycin can be improved by 0.24-4.6 times compared with a contrast sample.
Owner:NANTONG YIKAI MEDICAL DEVICES CO LTD
Construction method and use of Streptomyces roseosporus gene engineering bacteria
ActiveCN102146414AIncrease productionReduce manufacturing costBacteriaMicroorganism based processesEscherichia coliRibosomal protein E-L30
The invention provides a construction method and use of Streptomyces roseosporus gene engineering bacteria. The construction method comprises: cloning upstream and downstream accessory key genes dptE, dptF, dptG, dptH, dptI and dptJ of a nonribosomal peptide synthetases (NRPS) gene in a daptomycin gene cluster; and constructing recombinant plasmids by using an Escherichia coli-Streptomyces shuttle expression vector. The recombinant plasmids are transferred into Escherichia coli ET12567 to culture the ET12567 and the Streptomyces roseosporus together, the Streptomyces roseosporus is transformed by a combined transfer method, a transformant is screened by brulamycin resistance and polymerase chain reaction (PCR) is performed for further confirmation. The Streptomyces roseosporus gene engineering bacteria constructed by the invention can be directly used in the industrial production of daptomycin and can improve yield and reduce cost.
Owner:NANTONG YIKAI MEDICAL DEVICES CO LTD
Daptomycin high-producing strain and preparation method thereof
The invention belongs to the field of microbial pharmacy, and in particular relates to a daptomycin high-producing strain and a preparation method thereof. The invention aims to solve the technical problem that daptomycin is low-yield and difficult to be obtained. A technical scheme adopted by the invention to solve the problem provides a mutant strain of Streptomyces roseosporus named after Streptomyces roseosporus SCU and having a preservation number of CGMCC No.6356. The mutant strain can efficiently produce daptomycin, and is easy to be cultured; the preparation process of daptomycin is simple and efficient, can obtain high-purity daptomycin, and has good application prospect in the microbial pharmaceutical industry.
Owner:SICHUAN UNIV
Process for the production of daptomycin
The present invention relates to an improved process for the production of Daptomycin by fermentation with Streptomyces roseosporus, in the presence of n-decanal or Cuphea oil as sources of the n-decanoyl side chain. These reagents allow to reduce toxicity effects on the bacteria and to avoid the use of solvents in the feeding solution.
Owner:OLON
Method for preparing daptomycin by fermentation
The invention discloses a daptomycin high-yield strain and a method for preparing daptomycin by fermentation, and belongs to the technical field of biochemical engineering. In the invention, streptomyces roseosporus is utilized as starting bacterium and is treated by protolast fusion and gene recombination processes to form a high-yield mutagenized strain WKL-126. The high-yield mutagenized strain WKL-126 is preserved in the China general microbiological culture collection center (CGMCC) at present and an accession number is 3731. The invention also discloses a method for preparing daptomycinthrough adopting the strain WKL-126. Compared with the prior art, the method can realize that a fermentation quantity per unit is over 2000 mg / L.
Owner:SHANDONG LUBEI PHARMA
Process for the production of daptomycin
The present invention relates to an improved process for the production of Daptomycin by fermentation with Streptomyces roseosporus, in the presence of n-decanal or Cuphea oil as sources of the n-decanoyl side chain. These reagents allow to reduce toxicity effects on the bacteria and to avoid the use of solvents in the feeding solution.
Owner:OLON
Streptomyces roseosporus and method for producing daptomycin by utilizing combined precursor
ActiveCN102796680AGood technical effectExtensive culture conditionsBacteriaMicroorganism based processesMicroorganismStreptomyces
The invention discloses streptomyces and a method for producing daptomycin by utilizing the streptomyces. The strain is collected in China General Microbiological Culture Collection Center with the collection number of CGMCC No. 5956, the streptomyces CGMCC No. 5956 can be cultured under appropriate fermentation conditions, and a composition of decanoic acid and decyl aldehyde is added as a precursor for producing the daptomycin. By adopting the method for producing the daptomycin by utilizing the streptomyces, disclosed by the invention, a target product, namely the daptomycin has the advantages of high valence, high utilization rate of resources and low production cost, and is conductive to industrial large-scale production.
Owner:鲁南新时代生物技术有限公司
Method for producing daptomycin by fermentation
The invention provides a method for producing daptomycin by fermentation, characterized by in the fermental cultivation process of Streptomyces roseosporus, adding an aseptic composite amino acid solution in the fermentation solution. Compared with a process without adding the composite amino acid, the method allows the fermentation unit of daptomycin to increase by more than 10 %, the impurity ingredients of products are not changed obviously, simultaneously, the method has the advantages of simple production operation, low requirement of devices, and low cost, and is suitable for industrial production.
Owner:NEW FOUNDER HLDG DEV LLC +2
Mutants of fatty acid adenosine monophosphate (AMP) ligase with improved substrate affinities and application thereof
The invention relates to mutants of a fatty acid adenosine monophosphate (AMP) ligase and application of the mutants, and belongs to the field of bioengineering. The fatty acid AMP ligase comes from streptomyces roseosporus. The 296th glycine of the fatty acid AMP ligase is changed into alanine, and the 302th isoleucine of the fatty acid AMP ligase is changed into valine to respectively obtain the mutants pAL296 and pAL302. The mutants of the fatty acid AMP ligase can improve the binding level with exogenous precursor decanoic acid to enhance the yield of daptomycin. According to the invention, an encoding gene dptE of the fatty acid AMP ligase is subjected to site-directed mutagenesis in vitro by using computer simulation, overlap extension PCR and site-directed mutagenesis technologies to screen out the mutants pAL296 and pAL302 of which the affinities are obviously improved, recombinant shuttle plasmids pAK296 and pAK302 are constructed and sequentially led to the streptomyces roseosporus, and zygotes are screened to obtain streptomyces roseosporus DCE296 and DCE302 of the fatty acid AMP ligase with improved substrate affinities to lay a foundation for improving the production level of daptomycin.
Owner:CHINA PHARM UNIV
Method for producing Daptomycin by fed-batch methyl oleate fermentation
InactiveCN103695510ALow toxicityGuarantee the effect of flow plusMicroorganism based processesFermentationBiotechnologyEngineering
The invention provides a method for producing Daptomycin by fed-batch methyl oleate fermentation. A methyl oleate solution is supplemented into a fermentation tank in a Streptomyces roseosporus fermentation culture process to produce the Daptomycin. Thus, the method provided by the invention can enhance the yield of the Daptomycin. The method provided by the invention widens the path for producing Daptomycin by a fermentation process; and the methyl oleate solution can exist in the form of liquid at normal temperature, and thus, can not crystallize due to low temperature, thereby ensuring the fed-batch effect. Besides, the method is suitable for laboratory small-tank fermentation of Daptomycin, and also suitable for scale-up production in industrialized big tanks.
Owner:CHENGDU YATU BIOLOGICAL TECH
Daptomycin injectable formulation
InactiveUS20150216928A1Improve production stabilityShorten the timeAntibacterial agentsOrganic active ingredientsL-AspartateHydrolysate
The present invention disclose a lyophilized pharmaceutical formulation comprising antibacterial agent, daptomycin as active and tocopheryl phosphate hydrolysate mixture with improved reconstitution time for parental administration and to the process of preparation thereof. Daptomycin is a cyclic lipopeptide antibacterial agent derived from the fermentation of Streptomyces roseosporus. The chemical name is N-decanoyi-L-tryptophyl-Dasparaginyl-L-aspartyi-L-threonylglŷ D,-seryl-threo-3-methyl-L-glutamyl-3-anthraniloyl-L-alanines 1-lactone.
Owner:AGILA SPECIALTIES
Method for synthesizing key enzyme cofactor by adding daptomycin to improve daptomycin yield
InactiveCN101724674AIncrease productionEasy to operateMicroorganism based processesFermentationSporeStreptomyces
The invention relates to a method for synthesizing a key enzyme cofactor by adding daptomycin to improve the daptomycin yield, which comprises the following steps of: putting streptomyces reseosporus slant spores into sterile water to prepare a spore suspension at room temperature; then inoculating the 0.5-ml spore suspension into a 250ml shake flask filled with a 30ml seed culture medium at the temperature of 28-32 DEG C, and cultivating in a 180-220rpm shaking bed for 48 hours; then adding the mixture with a 1-percent inoculated dose into an automatic 7.5LDE fermentation tank filled with a fermentation culture medium; adding one or the composition of 0.5-30mg / l cofactor heme or calcium leucovorin or pyridoxal phosphate VB6; controlling the ventilation volume to be 0.8-1.2v / v / m at the temperature of 28-32 DEG C, and fermenting for 90-144 hours with a pH value of 6.5-7.5. The method is utilized for regulating biological enzyme activity, so that an intracellular metabolic flux leading to daptomycin synthesis is increased, and the yield of the daptomycin is improved; the method has simple operation and low cost, and the fermentation unit of the daptomycin in the fermented cultivated streptomyces reseosporus can be improved by 0.24-4.6 times than a reference substance.
Owner:TIANJIN UNIV
Novel method for adding decanoic acid in fermentation process of daptomycin
InactiveCN102703551AIncrease productionLow toxicityMicroorganism based processesFermentationFermentationStreptomyces roseosporus
The invention relates to a novel method for adding decanoic acid in the fermentation process of daptomycin, namly lipase and ethyl decanoate are simultaneously added in the fermentation cultivation process of streptomyces roseosporus, the ethyl decanoate is hydrolyzed by the lipase so as to add the precursor decanoic acid to produce the daptomycin, and the novel method is a method for improving the yield of the daptomycin. The method has the advantages that: the novel method for adding the decanoic acid is explored, the decanoic acid is slowly added by an enzymolysis method of the ethyl decanoate, and the toxicity of the decanoic on cells is reduced, so that the yield of the daptomycin is improved. The method comprises the following steps of: optimizing the addition amount of the ethyl decanoate and the lipase; and optimizing the addition time of the ethyl decanoate and the lipase. The yield of the daptomycin can be improved by when the novel method provided by the invention is used for producing the daptomycin.
Owner:CHINA PHARM UNIV
Method and application of overexpressing zwf2 gene to increase daptomycin production
InactiveCN102286497AIncrease productionReduce manufacturing costBacteriaMicroorganism based processesEscherichia coliPrimary metabolism
The present invention provides a method for overexpressing the zwf2 gene to increase the yield of daptomycin and its application, and clones a key enzyme 6-phosphate glucose dehydrogenase gene (zwf2) in the primary metabolic pentose phosphate pathway, using Escherichia coli-Streptomyces Shuttle plasmid expression vector construction of recombinant plasmids. The recombinant plasmid was introduced into Escherichia coli ET12567, ET12567 was co-cultured with Streptomyces roseospora, and Streptomyces roseospora was transformed by the combined transfer method, and then the transformants were screened by apramycin resistance, and the genetically engineered bacteria were further verified by PCR , thereby constructing the genetically engineered strain HP-2. The Streptomyces roseospora genetically engineered bacterium HP-2 constructed by the present invention has an 18% higher output than the starting strain, and the output of daptomycin is as high as 700mg / L, which can be directly used in the industrialized production of daptomycin, which can improve Yield reduces cost.
Owner:TIANJIN UNIV
Method for producing Daptomycin by fed-batch decyl aldehyde fermentation
InactiveCN103695509ALow toxicityGuarantee the effect of flow plusMicroorganism based processesFermentationBiotechnologyMicrobiology
The invention provides a method for producing Daptomycin by fed-batch decyl aldehyde fermentation. A decyl aldehyde solution is supplemented into a fermentation tank in a Streptomyces roseosporus fermentation culture process to produce the Daptomycin. Thus, the method provided by the invention can enhance the yield of the Daptomycin. The method provided by the invention widens the path for producing Daptomycin by a fermentation process; and the decyl aldehyde solution has low toxicity for cells and can exist in the form of liquid at normal temperature, and thus, can not crystallize due to low temperature, thereby ensuring the fed-batch effect. Besides, the method is suitable for laboratory small-tank fermentation of Daptomycin, and also suitable for scale-up production in industrialized big tanks.
Owner:CHENGDU YATU BIOLOGICAL TECH
Method utilizing fosfomycin to carry out breeding of daptomycin high-yield bacterial strains
InactiveCN104342379AAppropriate methodGood effectBacteriaMicroorganism based processesSporeScreening cultures
The invention discloses a method for obtaining daptomycin high-yield bacterial strains through screening streptomyces roseosporus, which is sensitive to fosfomycin, and belongs to the technology of bacterial strain breeding. The method comprises the following steps: dissolving spores cultured in a slope in sterile water to prepare a spore suspension, subjecting the spore suspension to a UV treatment, painting the suspension on a separated culture medium, picking the colonies growing on the culture medium by a sterile bamboo stick, then inoculating the colonies on solid screening culture mediums with different fosfomycin concentrations, selecting colonies that are sensitive to fosfomycin in different concentrations, inoculating the selected colonies on a slope culture medium to culture the colonies, then transferring the colonies to a liquid culture medium to carry out liquid culture in the end, and finally picking out the high-yield bacterial strains with stable genetic characters.
Owner:JIANSGU INST OF MICROBIOLOGY
Streptomyces roseospora and method for producing daptomycin using combined precursors
ActiveCN102796680BExtensive culture conditionsCan implement industrial productionBacteriaMicroorganism based processesSnow moldMicroorganism
The invention discloses a streptomycete and a method for producing daptomycin by using the streptomycete. The strain is preserved in the General Microorganism Center of China Microbial Strain Preservation Management Committee, and the preservation number is CGMCC No.5956. In the present invention, Streptomyces CGMCC No.5956 is cultivated under suitable fermentation conditions by adding capric acid and capric aldehyde composition as a precursor Fermentative production of daptomycin. By adopting the method for producing daptomycin by Streptomyces described in the present invention, the titer of the target product daptomycin is high, the resource utilization rate is high, and the production cost is low, which is beneficial to industrial scale production.
Owner:鲁南新时代生物技术有限公司
Method for producing daptomycin by fermentation
InactiveCN103695511AIncrease productionIncrease inhibitory concentrationMicroorganism based processesFermentationBiotechnologyMicrobiology
The invention provides a method for producing daptomycin by fermentation, and belongs to the field of production of daptomycin. In the method for synthesis of daptomycin by fermentation, the parameters such as the concentration and the inoculum size of a culture seed solution and pH of fermentation medium are optimized, the growth activity and the fermentation activity of streptomyces roseosporus are maintained, the production of the daptomycin is improved; in the fermentation process, a decanal solution is fed to the fermentation medium, and the adding time and the adding amount are optimized, so that the inhibition concentration of the daptomycin can be improved, and the synthetic production of the daptomycin is further improved.
Owner:CHENGDU YATU BIOLOGICAL TECH
Daptomycin fermentation culture medium and preparation method thereof
The invention discloses a daptomycin fermentation culture medium and a preparation method thereof. The fermentation culture medium comprises a 7.2-11g / 100mL carbon source , a 1.65-4.0 g / 100mL nitrogensource, 0.086-0.5g / 100mL inorganic salt and 0-0.1g / 100mL trace elements. The carbon source comprises maltodextrin and a carbon source A, and the dosage of maltodextrin is 7.2-9g / 100mL. The carbon source A is molasses or brown sugar and the dosage of the carbon source A is 0-1.8g / 100mL. The nitrogen source is one or more of pomegranatep flower yeast powder, soybean powder, bean pulp, peanut flourand feather powder. The fermentation culture medium for culturing streptomyces roseosporus can improve the yield of daptomycin and lowers the production cost greatly, and has a very good industrial application prospect.
Owner:SHANGHAI INST OF PHARMA IND +1
Construction method and use of Streptomyces roseosporus gene engineering bacteria
ActiveCN102146414BIncrease productionReduce manufacturing costBacteriaMicroorganism based processesEscherichia coliRibosomal protein E-L30
The invention provides a construction method and use of Streptomyces roseosporus gene engineering bacteria. The construction method comprises: cloning upstream and downstream accessory key genes dptE, dptF, dptG, dptH, dptI and dptJ of a nonribosomal peptide synthetases (NRPS) gene in a daptomycin gene cluster; and constructing recombinant plasmids by using an Escherichia coli-Streptomyces shuttle expression vector. The recombinant plasmids are transferred into Escherichia coli ET12567 to culture the ET12567 and the Streptomyces roseosporus together, the Streptomyces roseosporus is transformed by a combined transfer method, a transformant is screened by brulamycin resistance and polymerase chain reaction (PCR) is performed for further confirmation. The Streptomyces roseosporus gene engineering bacteria constructed by the invention can be directly used in the industrial production of daptomycin and can improve yield and reduce cost.
Owner:NANTONG YIKAI MEDICAL DEVICES CO LTD
Regulatory gene for improving utilization rate and tolerance of capric acid in streptomyces roseosporus and application of regulatory gene
PendingCN113717259ASolve problems with high workload and high blindnessIncrease profitBacteriaMicroorganism based processesCapric AcidMicrobiology
The invention discloses a regulatory gene for producing daptomycin by streptomyces roseosporus. The nucleotide sequence of the regulatory gene is shown as SEQ ID NO: 1, or the nucleotide sequence of the same protein as the nucleotide sequence shown as SEQ ID NO: 1. By using the global regulatory factor CRP, the problems of high workload and high blindness of traditional streptomyces breeding are solved, the daptomycin high-yield strain cultured by utilizing genetic engineering is obtained, and the application prospect is wide; and the method is used for transforming the starting strain streptomyces roseosporus, and it is accidentally found that the CRP gene can improve the utilization rate of the streptomyces roseosporus to the capric acid in the fermentation process and improve the tolerance of the streptomyces roseosporus to the capric acid.
Owner:ZHEJIANG UNIV OF TECH +1
Method for producing daptomycin by fermentation
Owner:NEW FOUNDER HLDG DEV LLC +2
Strain with high expression of daptomycin and its screening method
InactiveCN103937694BReduce blindnessImprove screening efficiencyBacteriaMicroorganism based processesMicroorganismScreening method
The invention relates to high-expression daptomycin strains and a screening method thereof, and belongs to the field of antibiotic production strains and screening thereof. The name of the classification of the strains is streptomyces roseosporus. The stains are preserved in the general microbiology center of the China Committee for Culture Collection of Microorganisms, with accession numbers being CGMCC NO.6899, NO.7014 and NO.7015. The invention also provides the screening method of the high-expression daptomycin strains. Ultraviolet mutagenesis and antibiotic resistance screening are combined to increase the mutation probability of the strains, so as to obtain the high-expression daptomycin strains. The output of each of the stains is higher than 59.86 mg / L and can reach 79.44 mg / L. The stains and the screening method can rapidly and effectively increase the production level of the daptomycin and have important practical significance.
Owner:INST OF BIOENG ACAD OF MILITARY MEDICAL SCI OF THE CHINESE
Streptomyces roseospora l31 with high daptomycin production and its construction method
ActiveCN107267434BIncrease supplyIncrease productionBacteriaMicroorganism based processesStreptomycesTryptophan
The present invention relates to a Streptomyces roseosporus (Streptomyces roseosporus) L31 with high yield of daptomycin, which fuses two enzymes (DptE and DptF) in the initial reaction of the synthesis pathway of daptomycin, and directional transforms tryptophan The production of daptomycin in this strain was increased by 140% compared with the original strain (WT).
Owner:ZHEJIANG UNIV
Method for preparing daptomycin by fermentation
The invention discloses a high-yield daptomycin strain and a method for preparing daptomycin by its fermentation method, belonging to the technical field of biochemical industry. The present invention uses Streptomyces roseosporus as the starting bacterium, and obtains a high-yielding mutagenic strain WKL-126 through protoplast fusion and gene recombination technology, which has been registered in the General Microorganism Center of China Microbiological Culture Collection Management Committee ( CGMCC), the preservation number is: 3731; the present invention also discloses a method for preparing daptomycin by using the strain, and compared with the existing method, the fermentation unit of the method reaches more than 2000 mg / L.
Owner:SHANDONG LUBEI PHARMA
Application of pleuromutilin for increasing yield of daptomycin
InactiveCN103243142ARealize industrial productionImprove efficiencyMicroorganism based processesFermentationMicrobiologyResistant strain
The invention discloses the application of pleuromutilin for increasing the yield of daptomycin. The application method comprises the following steps: screening anti-pleuromutilin streptomyces roseosporus by using pleuromutilin with an antiseptic concentration being higher than the lowest antiseptic concentration, further screening strains with increased daptomycin yield from the screened resistant strains, and obtaining high-yield strains through a stability test. When daptomycin is produced by using the resistant strains obtained by using the method disclosed by the invention, the yield is increased by about 30%, thereby laying a foundation for the industrial production of daptomycin.
Owner:SOUTHWEST UNIVERSITY
Screening method for breeding Streptomyces roseosporus strains producing Daptomycin and obtained strains
InactiveCN101892287BImprove screening efficiencyRaise the fermentation unitBacteriaMicrobiological testing/measurementStreptomycesWild type
Owner:SHANGHAI INST OF PHARMA IND CO LTD
Batch type feed-batch fermentation method for streptomyces roseosporus to produce Daptomycin efficiently
ActiveCN101824452BIncrease productionControllable fermentation processMicroorganism based processesFermentationSporeStreptomyces
The invention relates to a batch type feed-batch fermentation method for streptomyces roseosporus to produce Daptomycin efficiently, comprising the following steps: taking streptomyces roseosporus slant spore at normal temperature to prepare spore suspension by sterile water; inoculating 0.5ml of the spore suspension in a 250ml shake flask filled with 30ml of seed culture medium, and culturing for 48h in a shaker when the temperature is 28-32 DEG C and the revolution speed is 180-220 rpm; adding 1% of inoculum size in an automatic 7.5 LDE fermentation tank loaded with fermentation medium; adding one or combination of cofactor ferroheme or leucovorin or pyridoxal phosphate VB6 with the concentration of 0.5-30mg / L; and controlling the throughput to be 0.8-1.2v / v / m, the pH value to be 6.5-7.5 and fermenting for 90-144h at the temperature of 28-32 DEG C. By adopting the method in the invention to regulate biological enzyme activity to increase intracellular metabolism flux introduced in Daptomycin synthesis, the Daptomycin yield is improved; the method has simple operation and low cost; and in the streptomyces roseosporus fermented and cultured by the invention, the fermentation unit of the Daptomycin can be improved by 0.24-4.6 times compared with a contrast sample.
Owner:NANTONG YIKAI MEDICAL DEVICES CO LTD
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