82 results about "Batch fermentation" patented technology

The invention provides a genetically engineered bacterium for producing O-succinyl-L-homoserine as well as a construction method and application of the genetically engineered bacterium. In a chassis bacterium genome, the expression of a 2-ketoglutaric acid decarboxylase encoding gene sucA is enhanced, and the expression of a succinyl-coenzyme A synthetase encoding gene sucD is weakened, so that the supply of succinyl-coenzyme A is increased; the method comprises the following steps: increasing the NADPH (Nicotinamide Adenine Dinucleotide Phosphate) reducing capacity and ATP (Adenosine Triphosphate) energy supply of a chassis bacterium, increasing DNA (Deoxyribose Nucleic Acid) in combination with a transcription dual regulatory factor ompR to improve the stress resistance of escherichia coli under high osmotic pressure, and introducing an overexpression plasmid containing a homoserine transsuccinylase coding gene metA to construct the genetically engineered bacterium for producing O-succinyl-L-homoserine. The engineering strain obtained through a systematic metabolic engineering modification strategy can realize effective accumulation of OSH, the shake flask yield of OSH reaches 19.8 g / L, the fed-batch fermentation yield of a 5L fermentation tank reaches 110.5 g / L, the sugar-acid conversion rate reaches 52.6%, and a foundation is laid for subsequent construction of high-yield OSH engineering bacteria.

The invention provides a method for producing glycosyltransferase or sucrose synthase by fermenting recombinant escherichia coli, and belongs to the technical field of biological fermentation. According to the fermentation method provided by the invention, a three-stage material supplementing control fermentation strategy is adopted, namely after fermentation is carried out for 5 hours, material supplementing operation is started, the material supplementing speed is 6.24-7.20 g / L / h, fermentation is carried out for 8-10 hours, the material supplementing speed is reduced to 4.80 g / L / h, the temperature is reduced to 25 DEG C, and induction is carried out; then maintaining the material supplementing speed until the fermentation OD600 is 65-75, and then reducing the material supplementing speed to 3.84-4.80 g / L / h until the OD600 is not obviously increased any more; the material supplementing mode has remarkable advantages in the aspects of improving fermentation OD600 and fermentation enzyme activity, shortening the fermentation period, reducing the cost and the like.

The preparation method comprises the following steps: mixing salvia miltiorrhiza-schisandra chinensis superfine powder and roxburgh rose normal juice in a ratio of 3: 2: 5, carrying out composite enzymolysis and saccharomyces cerevisiae pretreatment, and sequentially carrying out aspergillus oryzae solid-state fermentation, acetobacter pasteurianus liquid-state index fed-batch fermentation and lactobacillus plantarum anaerobic flavor fermentation, so as to obtain the vinegar product with the homology of medicine and food. And parameters are regulated and controlled in real time through the three-layer stacked LSTM neural network. According to the invention, the conversion rate of tanshinone IIA to tanshinol reaches 65.8%, the total acid is greater than or equal to 7.2 g / 100mL, at least 21 flavor substances are contained, the batch difference rate is 4.2%, the energy consumption is reduced by 29.2%, the equipment utilization rate is increased by 50%, the product safety reaches the standard, and the method has a health-care function and palatability, and is suitable for industrial production.

The invention provides a combined type three-dimensional composting device, and relates to the technical field of waste resourceful treatment. A fermentation bag; a movable stacking rack; the fermentation shed is a telescopic shed body, the movable stacking frame is movably arranged in the fermentation shed, and a temperature detection device is further arranged in the fermentation shed. According to the invention, material loading and unloading can be carried out more conveniently, the space is fully utilized by adopting a stacking composting mode, sequencing batch fermentation can be carried out, air intake in the fermentation process can be controlled through the arrangement of the bidirectional air pipe, compost is fully fermented, the problem that the compost is not fully contacted with oxygen in the aerobic composting process is solved, and the aerobic composting efficiency is improved. And moreover, the device can be used for fermenting wastes on a large scale, the fermentation space is flexible and adaptive, and both the mounting convenience and the operation and maintenance cost are considered.

The invention discloses a method for constructing a high-yield natamycin engineering strain through overexpression of an extracellular transport protein gene pimA and a pathway specific regulation gene pimR, and the high-yield engineering strain is applied to fermentation production of natamycin. The yield of the natamycin can reach 19.49 g / L through fed-batch fermentation in a fermentation tank of 5L of the high-yield strain S.ilvosporeus pimA-pimR, and the yield of the natamycin is improved by 33.12% compared with the yield of a chassis strain S.ilvosporeus TUST01; the production intensity is improved by 33.33% compared with the production intensity of a chassis strain S.ilvosporeus TUST01, and the strain has a relatively high industrial application value.

The application discloses a construction method and application of a genetically engineered corynebacterium glutamicum for synthesizing a bacteriochlorophyllide amino acid shinorine, and belongs to the field of genetic engineering and fermentation technology. The genetically engineered corynebacterium glutamicum is constructed by taking corynebacterium glutamicum ATCC 13032 as a host strain, knocking out a competitive pathway gene, integrating a key enzyme gene in multiple copies on a genome, knocking out an acid production pathway gene and a serine dehydrogenase gene, and expressing a gene cluster for synthesizing shinorine on a plasmid, so that the synthesis yield of shinorine in a microbial cell is improved. The strain can produce shinorine in a flask, and 1.12 g / L of shinorine can be accumulated in 72 hours. In fed-batch fermentation in a 50 L fermenter, the strain can be cultured to 8.6 g / L.

This invention discloses a nicotinamide phosphoribosyltransferase mutant, a recombinant strain, and a method for constructing the same. The mutants are I457V, G344A, Q378A, T283G, or F182A, obtained by single-point mutation of the wild-type nicotinamide phosphoribosyltransferase shown in SEQ ID NO:1. This invention utilizes a method derived from... Schizotequatrovirus By rationally designing and site-directed mutagenesis of KVP40 nicotinamide phosphoribosyltransferase, combined with metabolic engineering to block the NMN degradation pathway and enhance substrate synthesis and product transport, the yield of β-NMN by the recombinant strain during shake-flask fermentation reached 4.82 g / L. Through optimization of fed-batch fermentation conditions, the highest yield of β-NMN during fed-batch fermentation in shake flasks reached 15.60 g / L.

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 application discloses a kind of high-yield O-succinyl-L-homoserine recombinant escherichia coli and its construction method and application, belong to genetic engineering and fermentation engineering technical field.The recombinant escherichia coli is expressed by expressing anti-feedback inhibition homoserine O-succinyltransferase metA fbr , aspartate ammonia-lyase aspA, aspartate transaminase aspC, 2 ketoglutarate decarboxylase sucA, dihydrothioctic acid succinyltransferase sucB and efflux protein yjeH, knock out metJ, improve intracellular NADPH availability, to enhance OSH synthesis pathway metabolic flow, precursor succinyl coenzyme A supply and product efflux.Using 5 L bioreactor for fed-batch fermentation, after fermentation 60 h, OSH production is as high as 137.4 g / L, and sugar acid conversion rate reaches 50.5%.The application provides engineering strain and technical realization path for the efficient fermentation of OSH.

The application discloses a genetically engineered bacterium for efficiently producing itaconic acid by using corn stalk hydrolysate and application thereof, and belongs to the technical field of gene recombination and metabolic engineering. The genetically engineered bacterium for efficiently producing itaconic acid by using corn stalk hydrolysate is characterized by the following aspects: taking a strain BW08 as a starting strain, heterologously expressing a homocentric acid decarboxylase gene CAD, deleting an isocitric acid dehydrogenase gene Icd, heterologously expressing a xylose acid dehydrase gene XD, a 2-keto-3-deoxy-xylose acid dehydrase gene KDXD and an alpha-ketoglutaric acid semialdehyde dehydrogenase gene KGSADH, and heterologously expressing a citric acid synthase gene gltA. In the fed-batch fermentation, the yield of itaconic acid of the genetically engineered bacterium reaches 68.6 g / L, and the conversion rate reaches 0.6 g / g (total sugar). The genetically engineered bacterium can efficiently metabolize corn stalk hydrolysate to produce itaconic acid.

The invention relates to the technical field of fermentation of medicinal material production, and discloses a preservation method of a pseudo-ginseng cell strain, which comprises the following steps: acquiring a working cell strain; obtaining a liquid culture medium; carrying out mixed culture on the working cell strain and the liquid culture medium, and dehydrating; and soaking the dehydrated biomass in a cryoprotectant, and then carrying out cryopreservation or refrigerated preservation. Through cryopreservation or refrigerated preservation of the mixed solution, the preserved working cell strain can be adopted for fermentation in real time according to the requirements of a user, the richness of the strain can be guaranteed, the preparation period of the seed solution is saved, multi-batch fermentation can be realized, and the yield is stable.

This invention discloses a method for constructing a high-succinic acid-producing Pichia pastoris cell factory, using Pichia pastoris (… Komagataella phaffii Using GS115 as the chassis, a reductive TCA cycle enhancement strategy and an sdh5 knockout strategy were first constructed, respectively. It was found that a single strategy was insufficient to effectively achieve succinic acid accumulation. Further, the two strategies were combined to obtain the engineered strain SAOG, which achieved succinic acid accumulation. Based on this, the malate transporter SpMAE was introduced to enhance the transmembrane transport capacity of succinic acid, and histidine auxotrophic recovery was combined to improve the growth and fermentation performance of the strain, resulting in the engineered strain SH, whose succinic acid accumulation was 25.1% higher than that of SAOG. Finally, the engineered strain SH achieved a succinic acid yield of 10.47 g / L in shake-flask fermentation and 112.6 g / L after 120 h of continuous fed-batch fermentation in a 5 L fermenter. This invention achieves efficient succinic acid synthesis in the Pichia pastoris chassis through the synergistic regulation of reductive TCA pathway enhancement, succinic acid oxidation blocking, enhanced transmembrane transport, and auxotrophic recovery, exhibiting stable fermentation performance, high yield, and good industrial application potential.

This invention discloses a high-yielding erythritol-producing *Yarrowia lipophila* strain (… Yarrowia lipolytica This invention relates to the field of biotechnology, specifically to *Yarrowia lipophila* CA20 as the starting strain, and its applications. A000039 A gene knockout method was used to construct a high-yield erythritol-producing *Yarrowia lipolytica* strain. The construction method provided by this invention is simple and of significant value in simplifying the construction process of high-yield strains. Furthermore, under the fermentation medium and conditions provided by this invention, the *Yarrowia lipolytica* strain producing high-yield erythritol was fed-batch fermented with glucose as a substrate, achieving a yield of 280.50 g / L and a yield of 0.71 g / g, demonstrating good economic benefits.

The invention provides a Trichoderma reesei engineering bacterium for high yield of beta-glucosidase, which is characterized in that a Trichoderma reesei SN1 strain is used as a starting strain, and an expression cassette for knocking out a cre1 gene, a constitutive expression cassette of an aspergillus niger source bglA gene expressed by a promoter cbh1 and a constitutive expression cassette of a 130442 gene expressed by the promoter cbh1 are constructed in a genome of the Trichoderma reesei SN1 strain. Through the knockout of the cre1 gene, the overexpression of the aspergillus niger source bglA gene and the overexpression of the 130442 gene, the yield of the beta-glucosidase in the trichoderma reesei is improved synergistically. Glucose is taken as a raw material, a transglycosylation reaction can be catalyzed by directly utilizing a crude enzyme solution of trichoderma reesei engineering bacteria with high yield of beta-glucosidase to prepare beta-disaccharide, and the beta-disaccharide can be taken as an inducer for cellulase production; a crude enzyme liquid with higher cellulase activity and beta-glucosidase activity is obtained by supplementing an inducer and carrying out fed-batch fermentation.

The invention relates to the field of gibberellin production, and discloses a genetically engineered bacterium for producing gibberellin GA3 at high yield as well as a construction method and application thereof. According to the invention, gibberellin GA3 high-yield genetically engineered bacteria are obtained by taking gibberellin as a chassis bacterium and enhancing expression of an AGP3 gene for coding amino acid permease, an FFUJ12592 gene for coding a transcription factor and a Lae1 gene for coding a global regulation factor in a genome of the chassis bacterium. Experiments prove that the GA3 yield of the constructed genetically engineered bacterium can reach 3.36 g / L after the culture medium is fermented for 168 hours and methyl linolenate fed-batch fermentation is carried out, and compared with the GA3 yield without gene modification or methyl linolenate fed-batch fermentation, the GA3 production capacity is remarkably improved.

A fermented natural substance having nitric oxide metabolites fixated and stabilized therein is produced by a process including adding a fermentative strain to nitrogen-containing natural substance and carrying out fermentation by a batch fermentation process. The nitrogen-containing natural substance is at least one selected from the group consisting of lettuce, Sedum sarmentosum, spinach, blueberry, dandelion, pomegranate, cabbage, garlic, Morinda citrifolia, onion, soybean, bean sprout, mulberry leaf, Momordica charantia, Rubus coreanus, Houttuynia cortada, aronia, Humulus japonicus, Coptis chinensis, hijiki, hooker chive, mushrooms, calamus, wild spinach (Seomcho), Chinese cabbage, kelp, apple, mugwort, orange, salmon testis, abalone shell, shellfish shell, cricket, silkworm, Rehmannia glutinosa, and Shipjeondaebo-tang. to Bacillus sp., Bifidobacterium sp., Enterococcus sp., or Lactobacillus sp.

The invention discloses a lysine total nutrient fed-batch fermentation method which comprises the following steps: adding a certain amount of culture medium into a fermentation tank, inoculating a seed solution, and fermenting; when the concentration of NH in the fermentation liquor is smaller than 2 g / L or the concentration of glucose is lower than 5 g / L, full-nutrient solution feeding is carried out, and the flow speed is 600 mL / (L.h); the total nutrient solution comprises an ammonium sulfate solution, a glucose solution and a second-generation culture medium; the concentration of the ammonium sulfate solution is 350g / L; the concentration of the glucose solution is 500g / L; the defects in the prior art are effectively overcome.

The invention provides a construction method and application of recombinant yarrowia lipolytica with high yield of salidroside, and belongs to the field of bioengineering. The recombinant yarrowia lipolytica with high yield of salidroside is named as a yarrowia lipolytica XJ-SAL strain, and after the recombinant yarrowia lipolytica XJ-SAL strain is subjected to fed-batch fermentation, the salidroside can be synthesized at a relatively high level. The construction method of the recombinant yarrowia lipolytica is easy to operate, and efficient synthesis of salidroside can be achieved.

The invention relates to the technical field of biological fermentation equipment, in particular to a continuous biological fermentation reactor. The invention aims to solve the technical problems of high energy consumption and low equipment utilization rate of the existing intermittent fermentation. According to the technical scheme, a plurality of isolators are arranged in a horizontal tank body, and the interior of the horizontal tank body is divided into a seed culture section, a production section and an aging section which are sequentially connected in series; sequential flowing of materials in the same functional section is achieved through the in-section communicating mechanism, and controllable isolation and one-way transfer between the functional sections are achieved through the inter-section material transfer mechanism; and the reaction process of a specific stage is enhanced through the in-stage reflux mechanism, and particularly, mature bacterial liquid at the tail end of the strain culture section is refluxed to the starting end so as to realize internal continuous regeneration of the strain. Through systematic innovation of structure and operation, a multi-stage fermentation process is integrated in single equipment, and long-period continuous steady-state production is realized, so that the number of times of empty can sterilization is remarkably reduced, the energy consumption is greatly reduced, and the comprehensive utilization rate of system facilities is greatly improved.

The invention provides a construction method and application of recombinant yarrowia lipolytica with high hydroxytyrosol yield, and belongs to the field of bioengineering. The recombinant Yarrowia lipolytica capable of producing the hydroxytyrosol at the high yield is named as a Yarrowia lipolytica XJ-HT strain, and after the recombinant Yarrowia lipolytica XJ-HT strain is subjected to fed-batch fermentation, the hydroxytyrosol can be synthesized at a relatively high level. The construction method of the recombinant yarrowia lipolytica is easy to operate, and efficient synthesis of hydroxytyrosol can be achieved.

The invention relates to a high-yield guanine engineering bacterium as well as a construction method and application thereof, and belongs to the technical field of gene engineering. The engineering bacterium for high yield of guanine takes E.coli W3110 as a starting strain, and promoters of mglB, mglC, mglA, guaB and guaA genes are replaced with trc promoters; ptsG, purR, gpt and guaD genes are not expressed; the method comprises the following steps: overexpressing glk, prsA, purF and ushA genes, and a TK2029 gene and a phnN gene which are optimized by codons; and the promoter of the atpIBEFHAGDC gene is replaced by a promoter of J23108. According to the invention, wild E.coli.W3110 is used as a chassis microorganism, and a glucose metabolism system is reconstructed; the ATP supply is optimized; a key enzyme gene of a purine synthesis route is enhanced and feedback inhibition is relieved; the biosynthesis pathway of guanine is enhanced; and the degradation pathway of guanine is blocked. The high-yield guanine engineering bacterium adopts a fed-batch fermentation method, can reach the yield of 10.9 g / L in a 5L fermentation tank for 52 hours, and has a relatively good industrial prospect.

The invention relates to a recombinant yarrowia lipolytica strain with high yield of astaxanthin as well as a construction method and application thereof. The preparation method comprises the following steps: expressing geranyl geranyl diphosphate synthase CrtE, phytoene synthetase / lycopene cyclase CrtYB, phytoene desaturase CrtI, 3-hydroxy-3-methylglutaryl CoA reductase tHMGR, beta-carotene ketolase CrtW, beta-carotene hydroxylase CrtZ, ATP (adenosine triphosphate) citrate lyase ACL, acetyl-CoA synthase ACS, choline kinase CK and inositol polyphosphate kinase IPK in host bacteria, so as to obtain a recombinant bacterium; the expression cassettes of farnesyl diphosphate synthase ERG20 and isopentenyl pyrophosphate isomerase IDI are obtained. Meanwhile, a photocatalytic material O-g-C3N4 / PEI is added to receive visible light excitation and generate reducing electrons, synthesis of intracellular NADPH is promoted, and then accumulation of astaxanthin is promoted. And continuous fed-batch fermentation is carried out in a 5L fermentation tank, so that the production performance of yarrowia lipolytica is greatly improved, and a foundation is laid for industrial production of high-value terpenoids.

The application discloses a construction method and application of Corynebacterium glutamicum for synthesizing shinorine, and belongs to the field of genetic engineering and fermentation technology. The Corynebacterium glutamicum ATCC 13032 is used as a starting strain, a competitive pathway gene is knocked out, an optimal exogenous enzyme is screened, and a key enzyme gene cluster is integrated in multiple copies on a genome, so that the synthesis yield of shinorine in the microbial cell is improved, and the strain can accumulate 0.63 g / L of shinorine in 72 hours in a flask. In fed-batch fermentation in a 50 L fermenter, the final yield of shinorine can reach 4.3 g / L.

The invention discloses an engineering strain for increasing supply of cofactors and application of the engineering strain in improving production of epsilon-polylysine, and belongs to the technical field of microbial genetic engineering. The method comprises the following steps: by taking streptomyces albus for producing epsilon-polylysine as an original strain, simultaneously connecting a nicotinic acid ribose phosphate transferase gene pncB, a phosphoenolpyruvate carboxylase gene pck and a pyruvate dehydrogenase gene pdh in the strain with a pIB139 vector by utilizing a homologous recombination method to obtain a recombinant plasmid vector pIB139-pncB-pck-pdh, and introducing the recombinant plasmid vector into a competent cell to obtain the recombinant plasmid vector pIB139-pncB-pck-pdh. The engineering bacterium BP3 is obtained. The shake flask epsilon-PL yield of the engineering bacterium BP3 reaches 1.61 g / L and is improved by 30.89% compared with that of an original strain; the yield of fed batch fermentation reaches 37.21 g / L, the yield reaches 4.85 g / (L.d), and the maximum thallus concentration DCW reaches 43.47 g / L.

The invention relates to the technical field of fermentation engineering, in particular to a fermentation method for improving the enzyme activity of C25 hydroxylase. Pichia pastoris, fed-batch fermentation and induced enzyme production strategies are combined, a heme precursor, ferrous sulfate heptahydrate and the like are added during fed-batch and induced enzyme production, and different temperatures and pH values of thallus growth and enzyme production are controlled, so that the enzyme activity of the C25 hydroxylase is remarkably improved finally.

The invention discloses a construction method and application of an engineering bacterium for increasing the yield of alpha-ketoglutaric acid. Wild E.coli.W3110 serves as a chassis strain, lactic dehydrogenase ldhA, pyruvate dehydrogenase poxB and formic acid C-acetyltransferase pflB are knocked out firstly, and the flow direction of pyruvic acid to lactic acid, acetic acid and formic acid is blocked; meanwhile, the promoter PBBaJ23109 is used for replacing a natural promoter of the sucA gene, so that alpha-ketoglutaric acid dehydrogenase is weakened, and the decomposition way of alpha-ketoglutaric acid is weakened; the phosphoenolpyruvate carboxylase ppc is overexpressed, and the flow direction of phosphoenolpyruvate to oxaloacetic acid is enhanced; isocitrate dehydrogenase icd from escherichia coli is overexpressed, so that synthesis of a product is promoted; besides, pyruvate dehydrogenase derived from saccharomyces cerevisiae is introduced and coded by genes PDB1, PDA1 and LAT1, so that an important precursor, namely pyruvic acid, is promoted to flow to acetyl coenzyme A; the engineering strain with high yield of alpha-ketoglutaric acid is finally obtained, the yield of 75.1 g / L can be achieved in a 5L fermentation tank through a fed-batch fermentation method for 40 hours, and the conversion rate is 39.6%.

The application relates to the technical field of biological catalysis, and particularly discloses a catalyst for acrylamide production and a preparation method thereof. The preparation method comprises the following steps: selecting a nitrile hydratase producing bacterium to perform fed-batch fermentation culture, and centrifuging to obtain wet sludge; sodium alginate and nano-titanium dioxide modified by a silane coupling agent are prepared into a composite carrier colloid; a bacterium suspension and the carrier colloid are mixed at a ratio of 1:3, and then are dropped into a calcium chloride solution containing glutaraldehyde to form; cross-linking is performed at low temperature by using glutaraldehyde; after washing, surface activation is performed in two steps; and finally, freeze-drying is performed to obtain solid catalyst particles. The method optimizes the whole process, the prepared catalyst has high reusability and high stability, is easy to separate from a product, and is suitable for continuous operation, solves the core defects of a traditional free bacterium catalyst, and takes into account the catalytic performance and industrial production efficiency.

The invention discloses kluyveromyces marxianus genetically engineered bacteria and application thereof, and belongs to the technical field of bioengineering. The invention discloses a kluyveromyces marxianus genetically engineered bacterium. The kluyveromyces marxianus genetically engineered bacterium is prepared by the following steps: firstly, screening to obtain a kluyveromyces marxianus strain with high ergosterol yield; on the basis, inducing and separating a MATa haploid strain; then, through the introduction of heterologous DHCR24 and DWF5 genes, the weakening of a competitive pathway gene ERG6, the improvement of the metabolic flux of a squalene pathway in a sterol synthesis process, the compartment engineering of a peroxisome region of a mevalonic acid pathway, the knockout of an hypoxia inhibition transcription factor ROX1, the improvement of cofactor supply, the optimization of a yeast lipid pathway and other metabolic engineering optimization reconstructions, the expression of the yeast lipid pathway is improved; and an engineering strain with high cholesterol yield is constructed and obtained. Through fed-batch fermentation, efficient and stable synthesis of cholesterol is achieved, the yield reaches 7.64 g / L, and a foundation is laid for biological manufacturing of cholesterol.

This application relates to the fields of bioengineering and fermentation technology, and discloses a genetically engineered *Escherichia coli* strain that synthesizes L-histidine and its preparation method. The engineered strain uses *Escherichia coli* W3110 as the starting strain and is modified... hisG Gene release from feedback inhibition; knockout ushA and nrdD Genes reduce precursor consumption; inactivation slyA Genes reduce energy waste; heterogeneous integration zwf and gnd Genes and replacement pgi The gene promoter redirects carbon flow to the pentose phosphate pathway, enhancing the supply of key precursors PRPP and reducing agent NADPH; introducing courtE Genes promote product efflux. Combined with an optimized fed-batch fermentation process, this invention effectively solves the problems of insufficient precursor supply, uneven energy distribution, and product inhibition through a systems metabolic engineering strategy, increasing L-histidine yield and sugar-acid conversion rate, making it suitable for industrial production.