209 results about "Biomanufacturing" patented technology

The invention discloses a high-performance carbonyl reductase mutant and application thereof in synthesis of a series of chiral alcohols. The high-performance carbonyl reductase mutant is obtained by performing the following mutations on an amino acid sequence as shown in SEQ ID NO.2: the 69th alanine mutates into any one of lysine, leucine, aspartic acid or asparagine, and the 69th alanine mutates into any one of lysine, leucine, aspartic acid or asparagine; and / or the 100th glycine is mutated into any one of glutamic acid, serine, lysine or asparagine. Compared with a wild type enzyme, the thermal stability and the catalytic activity of the obtained mutant are remarkably improved, particularly, single point mutants Mut-A69N, Mut-G100E and Mut-G100N and a combined mutant Mut-A69N-G100N show excellent relative enzyme activity, thermal stability and substrate tolerance. The mutant has high catalytic activity and stability to various chiral alcohols, and the contradiction that the traditional carbonyl reductase is easy to inactivate at high temperature and the catalytic efficiency is difficult to achieve at the same time is solved. The invention provides an efficient and stable enzyme catalysis tool for green biological preparation of chiral drug intermediates.

The invention belongs to the technical field of microbial genetic engineering, and particularly relates to an alpha-2, 3-sialyltransferase mutant and application thereof. The a-2, 3-sialyltransferase mutants V175N, P198A, G173D, D174Q, F196K and A315H are obtained by performing site-specific mutagenesis on six amino acids in an a-2, 3-sialyltransferase amino acid sequence coded by a gene derived from Campylobacter jejuni (OH4384), the yield of 3 '-sialyllactose is remarkably increased by single-point mutagenesis of the V175N, the yield of 3'-sialyllactose is remarkably increased by single-point mutagenesis of the V175N, the yield of 3 '-sialyllactose is remarkably increased by single-point mutagenesis of the P198A, the G173D, the D174Q, the F196K and the A315H, the optimal recombinant microbial strain 3 '-SL-09 (V175N / P198A / D174Q) is obtained through combination of multiple mutation sites, the yield can reach 5.91 g / L, the bottleneck problem of low catalytic efficiency of sialyltransferase is effectively solved, and an enzyme element with excellent performance is provided for high-efficiency and low-cost biological manufacturing of 3'-SL.

The invention discloses a method for constructing a multicellular living body material by adopting a droplet bioreactor, which belongs to the crossing field of biological materials and microbial engineering, and comprises the following steps: (1) resuspending different cells in different polymer solutions to prepare degradable or phase-separable hydrogel particles containing cells; (2) dispersing the hydrogel particles in a cross-linkable hydrogel matrix to form a composite hydrogel; and (3) curing the composite hydrogel, and then carrying out degradation treatment to obtain the liquid cavity structure multicellular system bioreactor with spatial partition and dynamic interaction characteristics. According to the invention, ordered distribution and metabolism synergy of different microorganisms in space can be realized, controllable degradability and excellent mass transfer performance are realized, bacterial slow release and metabolite exchange can be maintained, and the method is suitable for long-term stable operation of a continuous flow reactor. The method has wide application prospects in the fields of green biological manufacturing, renewable energy source production, environmental restoration, biomedical engineering and the like.

The invention relates to bacillus megatherium XW-02 (the preservation number is CCTCC NO: M 2025185), a microbial preparation of the bacillus megatherium XW-02, and application of the microbial preparation. The bacillus megatherium XW-02 has the advantages that the preservation number is CCTCC NO: M 2025185; the strain can efficiently express xylanase through xylan induction, hemicellulose in tobacco leaves is remarkably degraded, chemical composition is optimized, and combustion harmful substances are reduced. The treated cigar has the advantages that the aroma richness is improved, the purity is improved, the taste mellowness is improved, and the overall quality is improved by 1-2 grades. The xylan extracted from agricultural wastes is used as an inducer to construct a green biological manufacturing system, the cost is reduced by more than 80% compared with the traditional process, and the emission of three wastes is reduced. The process compatibility is high, the method can be matched with an existing production line only by additionally arranging a strain culture module, the single-line annual tobacco leaf treatment amount reaches 500 tons, and economic benefits are remarkable. The invention provides a safe, efficient and environment-friendly quality improvement solution for the tobacco industry, and has great industrialization value.

The invention relates to the technical field of textile bio-manufacturing and industrial process automation control, in particular to a bio-based fabric production temperature and humidity intelligent regulation and control system which comprises a data acquisition unit used for acquiring temperature and humidity sensor values in a fermentation curing workshop in real time and reading current heating power of an actuator and a fan rotating speed instruction; the reference state reconstruction unit is used for receiving the input state vector and generating an interference-free reference vector; the disturbance simulation unit is used for generating a theoretical damaged state vector representing a specific fault mode; the double-track difference unit is used for generating a real difference feature vector and a theoretical difference feature vector; the coupling regulation and control unit is used for calculating a similarity value of the real difference feature vector and the theoretical difference feature vector in a number domain space; according to the method, non-ideal factor interference is effectively eliminated, and the physical interpretability and numerical traceability of the reference data are ensured.

The invention belongs to the technical field of metabolic engineering and biological manufacturing, and particularly relates to an engineering bacterium for producing gallic acid (GA) and application of the engineering bacterium in production of gallic acid. According to the method, key metabolic nodes in the gallic acid production process are systematically regulated, for example, the hydroxylase activity is improved, the pyruvic acid flow direction is regulated, the aromatic amino acid precursor supply is improved, and the dynamic balance between the engineering bacterium growth and the gallic acid product synthesis is realized, so that the gallic acid yield and the carbon yield are remarkably improved. Experiments show that the gallic acid yield of the engineering bacteria prepared by the invention reaches 12.5 g / L in a shake flask experiment, and reaches 109.8 g / L in a 3 L fermentation tank; and the carbon yield is increased to 0.64 g / g glucose, which is the highest level reported in the current literature.

The invention discloses an SAM hydrolase mutant and application thereof, the specific activation effect of halogen anions (F <->, Cl <->, Br <-> and I <->) on SAM hydrolase (containing MJ1651 wild type and mutant) is found for the first time, and the active sequence of the SAM hydrolase is F <-> > I <-> > Br <-> = Cl <->. According to the method, 400 mM of halide salt is added into a reaction system, so that the catalytic efficiency is improved in a breakthrough manner; the yield of wild type enzyme adenosine is improved by 20-300% (optimally, an F-system); the yield of the mutant R89C is soaring up by nearly 6 times under the action of KF; the activity of the immobilized enzyme is still more than 90% after the immobilized enzyme is repeatedly used for 5 times. The method is easy and convenient to operate, green production is achieved with water as the solvent (three wastes are reduced by 90%), the comprehensive cost is reduced by 41%-80 / kg, and an efficient solution is provided for industrial biological manufacturing of antiviral drug intermediates and the like.

The invention discloses an escherichia coli engineering bacterium for producing 5-ALA by an anaerobic fermentation method as well as a construction method and a fermentation method of the escherichia coli engineering bacterium. The engineering bacterium is constructed by taking escherichia coli (E. coli) ZX11 as a host and performing heterologous expression on 5-ALA synthetase (HemA) from rhodobacter capsulatus. In order to improve the soluble expression level of the HemA, the HemA is subjected to fusion expression with a maltose binding protein (MBP) tag. Furthermore, the engineering bacterium can also heterologously express a visual purple protein (PR) fused with the MBP tag. The construction method of the engineering bacteria comprises the following steps: sequentially cloning the MBP-HemA fusion gene and the PR gene to an expression vector and transferring into host bacteria. By utilizing the engineering bacteria provided by the invention, anaerobic fermentation can be carried out in a culture medium taking glucose as a carbon source, and 5-ALA can be efficiently synthesized. The invention provides an effective way for realizing green and energy-saving anaerobic biological manufacturing of 5-ALA.

A method for monitoring a process of producing a multicellular structure from a population of cells in a 3D cell culture is described. The method comprises obtaining one or more 3D images of the 3D cell culture obtained by imaging the cell culture at different depths and / or from different angles, processing the one or more images to obtain a plurality of image-derived features, and determining values of one or more indicators indicative of progress or outcome of the maturation process using a statistical model, the statistical model is adapted to predict values of one or more indicators indicative of progress or outcome of the maturation process using an input comprising a plurality of image-derived features.

The invention discloses a high-industrial-property yarrowia lipolytica strain and application thereof, and belongs to the technical field of microbial engineering and fermentation. The mutant is derived from a natural bacterial strain of fermented vegetables, is obtained through high-throughput cell screening, has the advantages and characteristics of high salt resistance, low pH resistance, efficient utilization of an acetic acid substrate, high protein content, no need of vitamins for growth and the like, and is suitable for industrial production of microorganisms; the method can support efficient production of bio-manufactured products under strict conditions of acetic acid carbon source, no sterilization, no seawater, no vitamin and the like.

The invention belongs to the technical field of microbial genetic engineering, and particularly relates to an alpha-2, 6-sialyltransferase mutant and application thereof. The a-2, 6-sialyltransferase mutants M133L, E140D, D228H, N289D and G322Q are obtained by carrying out site-specific mutagenesis on five amino acids in an a-2, 6-sialyltransferase amino acid sequence coded by a gene derived from Photobacterium sp.JT-ISH-224, and compared with wild type alpha-2, 6-sialyltransferase, the yield of the single-point mutant 6 '-SL of the E140D and the yield of the single-point mutant 6'-SL of the G322Q are increased by 87.80% and 78.01% respectively. The yield of the optimal recombinant microbial strain 6 '-SL-7 (E140D / G322Q) obtained by mutation site combination can reach 1.471 g / L, the bottleneck problem of low catalytic efficiency of sialyltransferase is effectively solved, and an enzyme element with excellent performance is provided for high-efficiency and low-cost biological manufacturing of 6'-SL.

This invention relates to the fields of microbial genetic engineering and fermentation biomanufacturing technology, specifically disclosing a recombinant Corynebacterium glutamicum with high 5-aminolevulinic acid (ALA) production and its applications. Addressing the problems of existing strains such as crude enzyme activity regulation, inhibited cell growth, the need for external inhibitors, and low yield, this invention uses Corynebacterium glutamicum as a host and removes the gdhA gene without scarring to reduce precursor competitive metabolism. Site-directed mutations of the endogenous hemB gene (S288A, D128E, R231K) are performed to moderately reduce dehydratase activity. A high-expression plasmid pXMJ19-hemA containing the hemA gene from Rhodopsinus capsulatum is constructed and introduced into the modified strain to obtain a recombinant strain with optimized triple metabolism. This strain reduces product degradation without the need for external dehydratase inhibitors, does not affect cell growth, and achieves a yield up to 4.30 times higher than the control after 42 hours of fermentation, with ALA accumulation exceeding 8.9 g / L. The strain exhibits stable characteristics, the process is simple, and it has good industrial application value.

The present invention relates to a device for a scalable biomanufacturing platform for the production of modified cells such as CAR-modified T-cells while eliminating on-target / off-tumor toxicity and decreasing the current production cost by 500 times (per treatment), and to attendant methods. The includes a first chamber for proliferating a population of cells and a second chamber for modifying the cells to express a desired T-cell receptor antigen.

This invention discloses a recombinant vector, recombinant bacteria, and fermentation method for high-yield GHK production, belonging to the field of biomedical technology. The recombinant expression vector of this application comprises a bicistronic expression cassette controlled by a T7 / lac heterozygous promoter, sequentially containing the encoding (GHK). n The vector encodes the first cistron of the polypeptide and the second cistron, where n is an integer from 2 to 200. When this vector is transformed into *E. coli* BL21, the resulting recombinant bacteria can simultaneously express (GHK) after IPTG induction. n Polypeptides and trypsinogen. During fermentation, trypsinogen is activated and enables the processing of (GHK). n In situ enzymatic cleavage of peptides efficiently releases GHK. This invention integrates the traditional multi-step process into a "one-step fermentation," simplifying the production process and reducing purification difficulty. Examples show that the GHK yield can reach up to 3.9 g / L, providing an efficient and convenient new strategy for the large-scale biomanufacturing of GHK.

This invention discloses a strain of *Saccharomyces cerevisiae* and its application on baijiu (Chinese liquor) lees, relating to the field of biomanufacturing, specifically disclosing a strain of *Saccharomyces cerevisiae*. Meyerozyma guilliermondii This strain (BJZ-6, CGMCC No. 39087) can efficiently utilize xylose, tolerate inhibitors in baijiu (Chinese liquor) lees, and exhibits strong protein synthesis capabilities. This invention also provides a method for producing microbial protein from baijiu lees using liquid or solid-state fermentation with this strain. Through wet grinding pretreatment and enzymatic hydrolysis followed by fermentation, the entire component of the baijiu lees can be utilized, significantly increasing the crude protein and true protein content of the product. The strain and fermentation product can be used to prepare animal feed or feed additives.

Provided herein are integrated continuous biomanufacturing processes for producing a therapeutic protein drug substance. Also provided are systems that are capable of continuously producing a therapeutic protein drug substance.

The application discloses a biological implant robot machining posture planning and error compensation method based on a global stiffness model, belongs to the technical field of biological manufacturing and surgical robot auxiliary machining, and comprises the following steps: a biomechanical stiffness atlas covering the whole posture space of the implant is constructed by sparse modal sampling combined with an inverse distance weighting algorithm. The application effectively solves the problem that the cell responses are inconsistent due to the machining quality differences of different regions of the complex curved surface implant through the global surface biological activity consistency, and significantly improves the long-term success rate of implant surgery. The application is easy to deploy on the existing medical robot through hardware pollution. Through micron-level functional molding, the micron-level biological texture depth is accurately controlled, and the manufacturing level of the personalized implant is improved from simple geometric shape customization to a new height of surface biological function customization.

A bioreactor system for performing a biomanufacturing process is provided. The system includes a bioreactor vessel, an exhaust filter and an associated filter heater, and a height adjustment mechanism connected to the exhaust filter and the associated filter heater, and the bioreactor vessel. The exhaust filter is fluidly connected to a single-use bioreactor bag located within the bioreactor vessel via at least one tube, and a height adjustment mechanism adjusts the height of the exhaust filter and associated filter heater relative to the top surface of the single-use bioreactor bag. By adjusting the height of the exhaust filter and the associated filter heater, pipe kink is avoided, thereby ensuring that excessive pressurization of a single use bioreactor bag is avoided.

The present invention discloses an integrated bone and cartilage scaffold with a directional pore structure and a preparation method thereof, which belongs to the fields of tissue engineering, biomedicine and biomanufacturing technology. The method simulates the natural material and structure of bone cartilage, uses the principle of directional crystallization to prepare a bone and cartilage scaffold with a directional structure, and uses a low-temperature deposition manufacturing process based on rapid prototyping technology to prepare a horizontally oriented cartilage layer scaffold and a vertically oriented subchondral bone layer scaffold. Between the cartilage layer and the subchondral bone layer, methacrylated gelatin capable of UV cross-linking is combined with other materials with chemical grafting and bonding effects as a transition layer, thereby preparing a tissue engineering bone and cartilage integrated composite scaffold. The present invention is aimed at the treatment of articular bone and cartilage defects, and uses a bioactive material to manufacture a bone and cartilage composite scaffold with a directional pore structure. It can promote the coordinated repair of bone and cartilage tissue according to the characteristics of different functional areas of bone and cartilage, thereby improving the repair effect of bone and cartilage defects.

The present application belongs to the field of microbial metabolic engineering and synthetic biology technology application, in particular to a high methanol tolerance yeast chassis strain, a high 3-hydroxypropionic acid yield engineering bacterium and application. The high methanol tolerance yeast chassis strain takes wild type Pichia pastoris or fatty acid producing Pichia pastoris as a starting strain, is modified according to at least one of the following conditions (a)-(h), and a high methanol tolerance strain is obtained, wherein (a) MIOX gene knockout; (b) DMA2 gene knockout; (c) MET17 gene knockout; (d) BUB2 gene knockout; (e) CLB4 gene knockout; (f) UBP12 gene knockout; (g) ZFP gene knockout; (h) AOX1 gene mutation. The high methanol tolerance yeast chassis strain is further modified to obtain a high 3-hydroxypropionic acid yield engineering bacterium. The present application combines rational and non-rational metabolic engineering strategies, realizes efficient biosynthesis of fatty acids and 3-hydroxypropionic acid with methanol as the only carbon source, and lays an important foundation for low-carbon green biological manufacturing of chemicals.

The invention discloses a recombinant bacterium for producing mevalonic acid by taking glucose and acetone as co-substrates as well as a construction method and application of the recombinant bacterium, and belongs to the technical field of genetic engineering. The problems that an existing mevalonic acid biosynthesis mode is low in carbon atom economy, limited in theoretical yield and the like are solved. According to the invention, acetone carboxylase, acetoacetyl coenzyme A synthetase, 3-hydroxy-3-methylglutaryl coenzyme A reductase and hydroxymethyl glutaryl-CoA synthetase are subjected to heterologous expression in escherichia coli with an acetyl coenzyme A acetyltransferase gene atoB and a histidine protein kinase gene atoS knocked out, and self carbonic anhydrase is over-expressed; and a new way for synthesizing MVA by using glucose and acetone as a co-substrate is constructed. According to the method, one molecule of CO2 can be fixed in the biosynthesis of mevalonic acid, the yield of carbon atoms in the synthesis process of mevalonic acid is increased, the problem of low yield of carbon atoms in the synthesis process of mevalonic acid by taking glucose as a single substrate is solved, and a new thought is provided for constructing a carbon neutralization type biological manufacturing technology.

This invention discloses a method for the efficient synthesis of gastrodin using recombinant Corynebacterium glutamicum, belonging to the fields of genetic engineering, fermentation engineering, and synthetic biology. This invention uses Corynebacterium glutamicum as the host bacterium and knocks out… pobA The gene was expressed, and the engineered strain WN01 / pB6 was constructed using the expression plasmid pEC-XK99E to express cladoid-pyruvate lyase, carboxylic acid reductase, and glycosyltransferase, achieving heterologous synthesis of gastrodin. Further overexpression was then performed. aroG Genes, overexpression of protein-coding genes that activate carboxylic acid reductase sfp The engineered strain WN05 / pB6 was able to synthesize 7.37 g / L of gastrodin at the shake flask level, and the gastrodin yield reached 17.77 g / L at 72 h of batch fermentation in a 5-L fermenter, with a yield of 0.247 g / L / h. This provides a brand-new biomanufacturing platform for the industrial production of gastrodin.

The invention provides recombinant Escherichia coli for synthesizing heme and derivatives thereof, and the recombinant Escherichia coli is used for knocking out genes such as pyruvate oxidase poxB, pyruvate formate lyase pflB and porphyrinoperoxidase yfeX and enhancing genes such as phosphoenolpyruvate carboxylase ppc, glycerol transporter glpF and 3-phosphoglycerol dehydrogenase glpD, so that the heme and the derivatives thereof can be synthesized. After genes such as exogenous 5-aminolevulinic acid synthase hemA and ferrous chelating enzyme hemH are introduced, the heme and the derivatives thereof can be synthesized by taking glycerol as a raw material, and the heme has an application prospect in the field of biological manufacturing.

This invention discloses a pullulanase mutant with enhanced catalytic activity against highly branched dextrin substrates, its construction method, and its applications, belonging to the fields of enzyme engineering and biotechnology. This invention obtains two mutants, D139A and D139E, by site-directed mutagenesis of the pullulanase derived from Klebsiella pneumoniae at position 139 aspartic acid residue. Compared with the wild-type enzyme, both mutants maintain high hydrolytic activity against pullulan polysaccharides while significantly improving hydrolytic activity against dextrin substrates with high α-1,6 glycosidic bond content. Specifically, the hydrolytic activity against dextrin substrates with 6% and 10% α-1,6 bond content is increased by up to 242% and 110%, respectively. The pullulanase mutants obtained in this invention exhibit excellent catalytic performance in the enzymatic debranching reaction of highly branched dextrin substrates, showing promising application prospects in starch deep processing and related biomanufacturing fields.

This invention discloses a method for culturing skin organoids for large-scale production and the skin organoids used for large-scale production, belonging to the fields of tissue engineering and biomanufacturing technology. The method involves laying a dermal matrix layer composed of orthogonal double-network hydrogels embedding fibroblasts in a bioreactor containing multiple independently operable culture modules. After inoculating keratinocytes, negative pressure is used to drive a uniform descent of the culture medium level to achieve gas-liquid interface culture. The first network of the orthogonal double-network hydrogel is formed by photocrosslinking of methacrylamide recombinant collagen, and the second network is formed by Michael addition of thiolated polysaccharides and multi-arm polyethylene glycol maleimide. During the culture process, the barrier maturity is assessed in real time by online monitoring of transepithelial resistance, and the negative pressure is controlled accordingly. A single batch can produce 3000 cm³ of skin organoids. 2 The above-mentioned qualified skin organoids have a transepithelial resistance coefficient of variation of less than 10%.

The invention relates to the field of biological manufacturing, and particularly provides a hyaluronic acid fermentation process online monitoring method based on near infrared spectrum and multi-model fusion. The method comprises the following steps: constructing a near infrared spectrum online acquisition system in the hyaluronic acid fermentation process; collecting samples at different fermentation time points in different batches, and measuring the molecular weight; dividing a training set and a test set according to a certain proportion; preprocessing the original near infrared spectrum; constructing a plurality of basic models for prediction; optimizing hyper-parameters of the SVM model, the ANN model, the GBDT model and the RF model by using an improved umbrella-sky optimization algorithm which introduces a self-adaptive inertia weight strategy and an elite reverse learning strategy, and optimizing potential variable numbers of the PLS model by using a cross validation method; and a plurality of basic models are fused, and a multiple linear regression model is trained to generate final prediction. The method realizes real-time and accurate monitoring of the key parameter molecular weight in the hyaluronic acid fermentation process, and provides powerful technical support for optimizing the fermentation process and improving the yield and quality of hyaluronic acid.

The invention belongs to the cross technical field of cell engineering, nano-drugs and biological manufacturing, and particularly discloses a drug-loaded vesicle based on denucleated cells as well as a preparation method and application of the drug-loaded vesicle. According to the invention, a cell suspension and a cytoskeleton relaxant are co-incubated to relax an actin skeleton and weaken nucleoplasm connection; then loading the treated cell suspension on a multi-layer discontinuous density gradient centrifugal medium, realizing physical separation of cell nucleuses and cytoplasm through high-speed centrifugation according to buoyancy density difference, and collecting components of a specific interface to obtain high-purity denucleated cells with a complete membrane structure; then co-incubating the denucleated cells and ROS response type lipidosome (co-carrying therapeutic siRNA and a sound-sensitive agent Ce6) prepared in advance, so that the lipidosome is wrapped or anchored by a denucleated cell membrane; finally, the composite system is subjected to extrusion treatment through a microporous membrane, the drug-loaded vesicles uniform in particle size and stable in structure are obtained, and the drug-loaded vesicles are suitable for various application scenes such as anti-tumor treatment and RNA vaccine delivery.

The present invention relates to the viscosity reduction and stability enhancement of biotherapeutics in biomanufacturing and formulation. The method of viscosity reduction and stability enhancement comprises combining a biotherapeutic with a performance-enhancing excipient chosen from bis acetyl arginine, bis acetyl lysine, bis acetyl histidine, bis acetyl serine, bis acetyl proline, bis acetyl tryptophan, propionyl arginine, propionyl lysine, propionyl histidine, propionyl serine, propionyl proline, propionyl tryptophan, and mixtures thereof.

The application discloses a method for rapidly detecting amino acid content, which comprises the following steps: firstly, subjecting a substrate such as earthworm protein powder to microbial fermentation; and then rapidly detecting the free amino acid content in the fermentation liquor by means of an optimized indantrione color developing method (boiling water bath for 2-3 minutes, determination at 570 nm). The rapid detection technology is deeply combined with a strain screening process, and the amino acid production capacity of bacillus, lactic acid bacteria and mixed strains in a ratio of F14:MLB36:LAB2 (2:3:3) is utilized, so that high-quality strains capable of significantly improving the amino acid yield are directly screened. The application overcomes the problems of low efficiency and high cost of a traditional detection method, and provides a solution for efficient biological manufacturing and rapid detection of amino acids.

The invention belongs to the field of microbial engineering, and provides a gentamicin C1a high-yield biological manufacturing method based on metabolic network modeling and reverse metabolic engineering renovation, which comprises the following steps: S1, constructing a genome scale metabolic model of a target production strain, predicting and screening a first target gene in positive correlation with gentamicin biosynthesis by using the model; s2, performing whole genome sequencing on the gentamicin high-yield mutant strain, and identifying a second target gene related to the high-yield character through comparative genomics analysis; s3, combining the first target gene predicted in the step S1 and the second target gene identified in the step S2, and constructing to obtain a recombinant engineering strain; s4, carrying out fermentation culture on the recombinant engineering strain, and supplementing materials in the fermentation process; by remarkably improving the production efficiency and strain performance of gentamicin C1a, important technical support and theoretical basis are provided for green biological manufacturing of antibiotics.