Strain screening process for directional transformation of active ingredients in traditional Chinese medicine fermentation liquor

Abstract

The invention discloses a strain screening process for directional transformation of active ingredients in traditional Chinese medicine fermentation liquor. The strain screening process comprises the following steps: generating micro-droplets containing single colonies by adopting a micro-fluidic chip, wherein a culture medium in each droplet comprises the following components: 8-12g / L of tryptone, 4-6g / L of yeast extract, 18-25g / L of glucose and 0.05-0.2 g / L of actinomycete ketone; extracellular enzymes such as cellulase and protease secreted by microorganisms can efficiently decompose traditional Chinese medicine cell walls and destroy intercellular substance resistance, so that intracellular active ingredients are easier to dissolve out. For example, after the astragalus membranaceus is fermented, the dissolution rate of astragaloside is increased by multiple times, and the utilization rate of medicinal materials is increased by 30-50%. The bioavailability and the absorption efficiency are enhanced; macromolecular substances are converted into small molecules through strain metabolism, so that the intestinal absorption rate is obviously improved. For example, after ginsenoside Rg3 is fermented and converted into small molecules, the bioavailability is improved by 4-8 times, and the clinical effect is faster.

Description

Technical Field

[0001] The invention relates to a strain screening process, in particular to a strain screening process for directed conversion of active ingredients in traditional Chinese medicine fermentation liquor. Background Art

[0002] 1. Technical bottlenecks of traditional Chinese medicine fermentation:

[0003] Bacteria screening is highly blind:

[0004] Traditional fermentation relies on natural bacteria (such as naturally fermented koji in ceramic jars), resulting in unstable microbial community structures and large fluctuations in the conversion rate of the target active ingredient (±30%). For example, the production of light fermented black beans can cause genistein content to vary by over 40% due to contamination by foreign bacteria.

[0005] Mechanism defects: lack of adaptability to bacterial species (Γ), toxicity degradation ability (C tox )’s quantitative model cannot accurately match the characteristics of traditional Chinese medicine substrates.

[0006] Low efficiency of targeted conversion:

[0007] The microbial metabolic pathway is not clear, resulting in insufficient conversion rate (η) of active ingredients:

[0008] Saponin conversion: The conversion rate of ginsenoside Rb1 in traditional fermentation is only 15–20% due to the lack of β-glucosidase-specific strains;

[0009] Toxic residues: The degradation rate of diester alkaloids after fermentation of aconite is less than 60%, and the safety risk is prominent.

[0010] Process control relies on experience: Solid-state fermentation relies on empirical judgment based on “observing the color and smelling the aroma of the fermented koji”, and cannot dynamically optimize parameters:

[0011] Loss of control over key parameters: pH and temperature fluctuations lead to a 50% drop in Ganoderma triterpenoid production;

[0012] End point determination is ambiguous: the fermentation termination time error is ±24 hours, and the product yield is lost by 35%.

[0013] 2. Application limitations of modern biotechnology:

[0014] Functional limitations of a single strain:

[0015] Traditional pure strain fermentation (such as Aspergillus niger NJ-15) can only decompose the cell wall but cannot simultaneously activate the glycoside hydrolase system, resulting in less than a 2-fold increase in the bioavailability of astragaloside IV.

[0016] The design of composite bacterial consortium lacks interaction model (ψ), and the combination of Monascus and Bacillus is inhibited by competition (σ ij ≥0.5) leading to interruption of metabolic relay.

[0017] Inefficient screening technology:

[0018] The plate separation method takes 14–21 days and has a screening miss rate of >60% (e.g., vincristine-producing bacteria);

[0019] The lack of a high-throughput integrated microfluidic system makes it impossible to monitor the correlation between ΔOD and η in real time.

[0020] Lack of quality evaluation system:

[0021] Pharmacopoeia standards only test a single component (such as aflatoxin) and ignore the dynamic changes in metabolomics fingerprints;

[0022] New active substances in fermentation products (such as fermented Yupingfengsan immune peptides) cannot be quantified due to the lack of standard samples.

[0023] Therefore, there is an urgent need on the market for a better strain screening process for the targeted transformation of active ingredients in traditional Chinese medicine fermentation broth. Summary of the Invention

[0024] The technical problem to be solved by the present invention is to overcome the defects of the above-mentioned technology and provide a strain screening process for the directional conversion of active ingredients in traditional Chinese medicine fermentation broth.

[0025] To solve the above technical problems, the technical solution provided by the present invention is a strain screening process for the targeted conversion of active ingredients in traditional Chinese medicine fermentation broth, comprising:

[0026] A microfluidic chip was used to generate microdroplets containing single colonies. The culture medium in the droplets consisted of 8–12 g / L tryptone, 4–6 g / L yeast extract, 18–25 g / L glucose, and 0.05–0.2 g / L cycloheximide.

[0027] The target strain adaptability evaluation model is:

[0028]

[0029] in:

[0030] Γ is the strain fitness integral;

[0031] μ max is the maximum specific growth rate;

[0032] S is the substrate concentration;

[0033] C tox It is a traditional Chinese medicine toxicity inhibitor.

[0034] As an improvement, the strain screening objective function is defined as the active ingredient conversion rate η:

[0035]

[0036] The screening criteria require η ≥ 65%, and the bacterial growth kinetics meet the following requirements:

[0037]

[0038] X is the bacterial concentration, X max is the maximum load density.

[0039] As an improvement, microfluidic high-throughput screening methods are also included, including:

[0040] The target OD value screening interval of the droplet is 1.20≤OD 600 ≤2.50, positive droplet determination formula:

[0041]

[0042] The functional screening medium contained sodium carboxymethylcellulose (2 g / L) or pectin (1 g / L), and the color reaction threshold ΔOD ≥ 0.5.

[0043] As an improvement, the nitrogen source ratio and carbon-nitrogen balance equation are optimized:

[0044]

[0045] Among them C glucose =20g / L, C acetate =25g / L.

[0046] As an improvement, it also includes: bacterial symbiotic synergistic effect model, including:

[0047] Multi-species interaction gain coefficient ψ:

[0048]

[0049] k i is the active conversion efficiency of strain i;

[0050] σ ij Competitive inhibitory factor.

[0051] As an improvement, the fermentation condition control parameters are also included:

[0052] Feedback control equation for dynamic regulation of temperature and pH:

[0053] T(t)=T0+k p ·(pH target -pH(t)

[0054] T0=30℃,k p is the proportional gain coefficient.

[0055] As an improvement, the process for improving the purity of the target active ingredient includes:

[0056] Calculation of the yield ζ in the separation and purification stage:

[0057]

[0058] r prod is the product formation rate, M pure The mass of the purified product.

[0059] As an improvement, the strain stability verification method is also included, including:

[0060] Passage Adaptive Decay Model:

[0061]

[0062] λ is the decay constant, requiring the 10th generation

[0063] As an improvement, it also includes: Chinese medicine substrate pretreatment process,

[0064] The particle size distribution of raw materials meets the normal distribution where μ d =90 mesh, σ d ≤10 mesh;

[0065] Relationship between enzymatic hydrolysis efficiency∈ and particle size:

[0066]

[0067] d is the particle diameter, d min =0.1mm.

[0068] As an improvement, the product activity detection standard is also included:

[0069] HPLC was used to detect the content of target components, with a signal-to-noise ratio (SNR) ≥ 10:1;

[0070] Microbial residue ≤10 2 CFU / mL, meeting:

[0071]

[0072] D value The sterilization time is decremented.

[0073] Compared with existing technologies, this invention significantly improves the extraction rate and efficacy of active ingredients. Extracellular enzymes such as cellulase and protease secreted by microorganisms can efficiently decompose the cell walls of traditional Chinese medicines (such as cellulose and hemicellulose), destroying intercellular matrix resistance and facilitating the dissolution of intracellular active ingredients (such as saponins and flavonoids). For example, after fermentation, the dissolution rate of astragaloside IV in astragalus membranaceus increases several times, and the utilization rate of active ingredients increases by 30–50%.

[0074] Enhanced bioavailability and absorption efficiency: Bacterial metabolism converts macromolecules (such as polysaccharides and glycosides) into small molecules (such as aglycones), significantly improving intestinal absorption. For example, after ginsenoside Rg3 is fermented and converted into small molecules, its bioavailability increases 4–8 times, resulting in faster clinical efficacy.

[0075] Targeted degradation of toxic components to improve safety: Specialized strains of bacteria (such as Aspergillus niger) can modify or decompose toxic groups in traditional Chinese medicines. For example, fermentation of diester alkaloids in aconite reduces their toxicity by 40%, while preserving their active ingredients, ensuring safe use.

[0076] Catalytic production of novel active compounds: Microbial metabolic pathways can restructure the components of traditional Chinese medicines, generating new active substances not found in the original medicinal materials. Typical examples include the production of five new antimicrobial compounds from Panax notoginseng root fibers by Bacillus subtilis fermentation, and the production of lovastatin, a lipid-lowering compound, by fermentation using Monascus purpureus.

[0077] Achieving precise and targeted conversion of active ingredients: Through the synergistic integration of complex bacterial communities (e.g., Monascus + Bacillus natto + Bacillus) and AI dynamic control technology, the optimal metabolic window is locked. Experiments have shown that fermenting Astragalus with these complex bacterial species can increase the content of calycosin isoflavones by 3.8 times, with conversion specificity exceeding 90%.

[0078] Reduce production costs and promote industrialization: Intelligent fermentation systems (such as space-grade fermentation chambers) combined with strict strain stability control (activity of the 10th generation remains ≥86.7%) reduce contamination by foreign bacteria and strain re-screening costs, and increase production efficiency by 50% compared to traditional processes.

[0079] This process breaks through the technical bottlenecks of conversion efficiency and safety of traditional Chinese medicine ingredients through precise matching of bacterial strains, enzyme systems and metabolic targets, providing core support for the research and development of innovative traditional Chinese medicines. BRIEF DESCRIPTION OF THE DRAWINGS

[0080] Figure 1 It is a schematic diagram of the strain screening process for the directional transformation of active ingredients in the traditional Chinese medicine fermentation broth of the present invention. DETAILED DESCRIPTION

[0081] To facilitate understanding of the present application, the present application will be described more fully below with reference to the accompanying drawings. The accompanying drawings provide embodiments of the present application. However, the present application may be implemented in many different forms and is not limited to the embodiments described herein. Rather, these embodiments are provided to make the disclosure of the present application more thorough and comprehensive.

[0082] Unless otherwise defined, all technical and scientific terms used herein have the same meaning as those commonly understood by those skilled in the art to which this application pertains. The terms used herein in the specification of this application are for the purpose of describing specific embodiments only and are not intended to limit this application.

[0083] It will be understood that spatial relational terms such as "under," "beneath," "beneath," "under," "above," "above," etc., may be used herein to describe the relationship of an element or feature shown in the figures to other elements or features. It will be understood that in addition to the orientations shown in the figures, spatial relational terms also include different orientations of the device in use and operation. For example, if the device in the drawings is turned over, the element or feature described as "under" or "beneath" or "beneath" the other elements will be oriented as "above" the other elements or features. Thus, the exemplary terms "under" and "under" may include both the above and below orientations. In addition, the device may also include alternative orientations, such as, rotated 90 degrees or other orientations, and the spatial descriptors used herein are to be interpreted accordingly.

[0084] It should be noted that when an element is considered to be "connected" to another element, it can be directly connected to the other element or connected to the other element through an intermediate element. In the following embodiments, "connection" should be understood as "electrical connection", "communication connection", etc., if the connected circuits, modules, units, etc. can transmit electrical signals or data to each other.

[0085] When used herein, the singular forms "a", "an", and "the" may also include the plural forms, unless the context clearly indicates otherwise. It should also be understood that the terms "include / comprise" or "have" and the like specify the presence of stated features, integers, steps, operations, components, parts, or combinations thereof, but do not preclude the possibility of the presence or addition of one or more other features, integers, steps, operations, components, parts, or combinations thereof.

[0086] In conjunction with the attached drawings, the strain screening process for the directional transformation of active ingredients in traditional Chinese medicine fermentation broth includes:

[0087] A microfluidic chip was used to generate microdroplets containing single colonies. The culture medium in the droplets consisted of 8–12 g / L tryptone, 4–6 g / L yeast extract, 18–25 g / L glucose, and 0.05–0.2 g / L cycloheximide.

[0088] The target strain adaptability evaluation model is:

[0089]

[0090] in:

[0091] Γ is the strain fitness integral;

[0092] μ max is the maximum specific growth rate;

[0093] S is the substrate concentration;

[0094] C tox It is a traditional Chinese medicine toxicity inhibitor.

[0095] As an improvement, the strain screening objective function is defined as the active ingredient conversion rate η:

[0096]

[0097] The screening criteria require η ≥ 60%, and the bacterial growth kinetics meet the following requirements:

[0098]

[0099] X is the bacterial concentration, X max is the maximum load density.

[0100] As an improvement, microfluidic high-throughput screening methods are also included, including:

[0101] The target OD value screening interval of the droplet is 1.20≤OD 600 ≤2.50, positive droplet determination formula:

[0102]

[0103] The functional screening medium contained sodium carboxymethylcellulose (2 g / L) or pectin (1 g / L), and the color reaction threshold ΔOD ≥ 0.5.

[0104] As an improvement, the nitrogen source ratio and carbon-nitrogen balance equation are optimized:

[0105]

[0106] Among them C glucose =20g / L, C acetate =25g / L.

[0107] As an improvement, it also includes: bacterial symbiotic synergistic effect model, including:

[0108] Multi-species interaction gain coefficient ψ:

[0109]

[0110] k i is the active conversion efficiency of strain i;

[0111] σ ij Competitive inhibitory factor.

[0112] As an improvement, the fermentation condition control parameters are also included:

[0113] Feedback control equation for dynamic regulation of temperature and pH:

[0114] T(t)=T0+k p ·(pH target -pH(t)

[0115] T0=30℃,k p is the proportional gain coefficient.

[0116] As an improvement, the process for improving the purity of the target active ingredient includes:

[0117] Calculation of the yield ζ in the separation and purification stage:

[0118]

[0119] r prod is the product formation rate, M pure The mass of the purified product.

[0120] As an improvement, the strain stability verification method is also included, including:

[0121] Passage Adaptive Decay Model:

[0122]

[0123] λ is the decay constant, requiring the 10th generation

[0124] As an improvement, it also includes: Chinese medicine substrate pretreatment process,

[0125] The particle size distribution of raw materials meets the normal distribution where μ d =90 mesh, σ d ≤10 mesh;

[0126] Relationship between enzymatic hydrolysis efficiency∈ and particle size:

[0127]

[0128] d is the particle diameter, d min =0.1mm.

[0129] As an improvement, the product activity detection standard is also included:

[0130] HPLC was used to detect the content of target components, with a signal-to-noise ratio (SNR) ≥ 10:1;

[0131] Microbial residue ≤10 2 CFU / mL, meeting:

[0132]

[0133] D value The sterilization time is decremented.

[0134] 1. Implementation of microfluidic high-throughput screening system:

[0135] Implementation steps:

[0136] Microdroplet generation:

[0137] A microfluidic chip made of PDMS was used, with a droplet generation unit channel width of 50 μm, an oil phase flow rate of 0.5 mL / min, a water phase flow rate of 0.1 mL / min, and a generated droplet diameter of 80 ± 5 μm.

[0138] Culture medium formula: tryptone 10 g / L, yeast extract 5 g / L, glucose 22 g / L, cycloheximide 0.1 g / L, pH 6.8, injected into the aqueous phase inlet of the chip after sterilization.

[0139] Evaluation of strain adaptability:

[0140] Adaptive integration model Follow these steps to apply:

[0141] μ max By OD 600 Growth curve fitting Monod equation Get;

[0142] C tox (Toxicity inhibitory factor) Calculation of berberine residual rate in fermentation broth by HPLC detection: berberine initial concentration current concentration

[0143] Implementation case: Ganoderma lucidum strain GL-7 was inoculated, and Γ was measured at t0=0h and t=72h to be 18.7 (the threshold Γ≥15 is qualified).

[0144] 2. Verification of target component conversion rate:

[0145] Implementation process:

[0146] Conversion rate calculation and screening:

[0147] Conversion rate formula middle:

[0148] C initial is the initial concentration of astragaloside IV (1.2 mg / mL as determined by HPLC);

[0149] Cfinal is the concentration after fermentation (Example: Aspergillus niger AN-3 fermented for 96h and rose to 2.1mg / mL), so (satisfying η≥65%).

[0150] Growth dynamics control:

[0151] Growth equation Parameter settings:

[0152] X max =8.5g / L (based on the carbon-nitrogen ratio of the culture medium limited;

[0153] X (bacteria concentration) is monitored in real time by an online biosensor, and feeding is automatically performed when X ≥ 7.0 g / h.

[0154] 3. Symbiotic bacterial community collaborative fermentation:

[0155] Implementation plan:

[0156] Application of multi-species interaction model: gain coefficient According to the following configuration:

[0157] Bacterial combination: Lactobacillus LB-2 (k1 = 0.8) and yeast Y-9 (k2 = 0.6), competitive inhibition factor σ 12 =0.3;

[0158] Fermentation 48h (ψ>1.0 indicates synergistic effect).

[0159] 4. Dynamic parameter feedback control:

[0160] Hardware and algorithm implementation:

[0161] Temperature-pH linkage control:

[0162] Equation T(t) = 30 + k p ·(pH target -pH(t))

[0163] k p =2.5 (proportional gain coefficient, calibrated by Ziegler-Nichols tuning method);

[0164] When the real-time pH drops from 6.8 to 6.3, T(t) = 30 + 2.5 x (6.5 - 6.3) = 30.5°C.

[0165] Raw material pretreatment optimization:

[0166] Enzyme hydrolysis efficiency formula application:

[0167] Astragalus raw material is crushed to μm d =90 mesh, mesh σ d =8 mesh (satisfies normal distribution);

[0168] Take k = 12.5, d min =0.1mm, when d = 0.15mm∈ = 1-e -12.5×0.05 =0.46.

[0169] 5. Product purification and strain stability verification:

[0170] Key steps:

[0171] Purification yield calculation:

[0172] Yield Model middle:

[0173] r prod Monitored by online mass spectrometry, M pure After purification by macroporous resin, the weight was weighed (Example: Astragaloside IV ).

[0174] Generation decay model:

[0175] Attenuation equation verify:

[0176] Aspergillus niger AN-3 initial λ=0.015, 10th generation (qualified).

[0177] Sterility testing standards:

[0178] Microbial Residue Formula middle:

[0179] D value =1.5min (sterilization at 121℃), t steril =15min That is N res ≤10 -8 CFU / mL.

[0180] Implementation Case Data Summary Table

[0181]

[0182] 1. Significantly improve the conversion rate of active ingredients:

[0183] Improved directional transformation efficiency: through microfluidic high-throughput screening model (claims 1 and 3), combined with strain adaptability integration model Accurately screen highly active strains, with a target ingredient conversion rate η≥75% (such as astragaloside IV), which is 30–50% higher than traditional fermentation.

[0184] Microbial enzyme systems (such as cellulase and protease) efficiently decompose the cell walls of traditional Chinese medicine, releasing active ingredients within the cells, and increasing the extraction rate by more than 40%.

[0185] Production of novel active metabolites: The bacterial symbiosis model (claim 5) achieves multi-bacterial synergy through a gain coefficient ψ>1.0, promotes the production of secondary metabolites (such as new flavonoids), and enhances the pharmacological activity by 31% (implementation case).

[0186] 2. Reduce toxicity and improve safety:

[0187] Directed degradation of toxic components: C in the adaptive model tox (toxicity inhibitory factor) real-time monitoring, combined with Aspergillus niger and other strains to degrade diester alkaloids (such as the toxicity of aconite is reduced by 40%), to ensure the safety of medication.

[0188] Sterilization residue control (claim 10) meets log 10 (N res )≤-8(ie N res ≤10 -8 CFU / mL), which meets the sterility standards of pharmacopoeia.

[0189] 3. Enhance the bioavailability of drugs:

[0190] Small molecule conversion and rapid absorption: bacterial metabolism degrades macromolecules such as saponins and polysaccharides into small molecules (for example, the conversion rate of ginsenoside Rg3 is increased by 4-8 times), and the intestinal absorption rate is increased by 2-5 times.

[0191] Liquid fermentation technology shortens the cycle to 72–96 hours, and its efficiency is 50% higher than that of solid fermentation.

[0192] 4. Precise control to achieve targeted transformation:

[0193] Dynamic parameter optimization: temperature-pH feedback control (claim 6) T(t) = T0 + k p The ΔpH fluctuation range is ±0.1, maintaining stable enzyme activity.

[0194] The carbon-nitrogen balance equation C / N∈[5,8] (claim 4) optimizes the bacterial density X max =8.5g / L, ensuring metabolic efficiency.

[0195] 5. Process innovation promotes industrialization:

[0196] Stability and cost control: generation attenuation model Ensure that the activity of the 10th generation remains at 86.7% (λ≤0.015), reducing the cost of strain rescreening.

[0197] Raw material particle size control (claim 9)∈=1-e -k·(d-0.1) Improve enzymatic hydrolysis efficiency by 46% and reduce raw material loss.

[0198] 6. Application expansion creates diversified value:

[0199]

[0200] Summarize:

[0201] This process achieves simultaneous improvements in active ingredient conversion rate, safety, and efficacy through precise strain screening (high-throughput model), dynamic metabolic regulation (mathematical optimization model), and targeted toxicity degradation, while also promoting the standardization and industrialization of traditional Chinese medicine fermentation. Its core value lies in:

[0202] Scientific breakthrough: Integrating microfluidics, fermentation dynamics, and mathematical models to address the blindness of traditional screening;

[0203] Industrial value: Reduce production costs by 30%, shorten R&D cycle by 50%, and support the application of innovative Chinese medicines.

[0204] Summary of improvements to key technical indicators:

[0205]

[0206] The present invention and its embodiments are described above. This description is not restrictive. The drawings show only one embodiment of the present invention, and the actual structure is not limited thereto. In short, if a person skilled in the art is inspired by this and, without departing from the purpose of the present invention, designs structures and embodiments similar to this technical solution without inventiveness, they shall fall within the scope of protection of the present invention.

Claims

1. A strain screening process for directed conversion of active ingredients in traditional Chinese medicine fermentation broth, characterized by: A microfluidic chip was used to generate microdroplets containing single colonies. The culture medium in the droplets consisted of 8–12 g / L tryptone, 4–6 g / L yeast extract, 18–25 g / L glucose, and 0.05–0.2 g / L cycloheximide. The target strain adaptability evaluation model is: in: Γ is the strain fitness integral; μ max is the maximum specific growth rate; S is the substrate concentration; C tox It is a traditional Chinese medicine toxicity inhibitor.

2. The strain screening process for directed conversion of active ingredients in a traditional Chinese medicine fermentation broth according to claim 1, characterized in that: The objective function of strain screening is defined as the active ingredient conversion rate η: The screening criteria require η ≥ 65%, and the bacterial growth kinetics meet the following requirements: X is the bacterial concentration, X max is the maximum load density.

3. The strain screening process for directed conversion of active ingredients in a traditional Chinese medicine fermentation broth according to claim 2, characterized in that: Also included are microfluidic high-throughput screening methods, including: The target OD value screening interval of the droplet is 1.20≤OD 600 ≤2.50, positive droplet determination formula: Functional screening medium contained sodium carboxymethylcellulose (2 g / L) or pectin (1 g / L), and the color reaction threshold ΔOD ≥ 0·5.

4. The strain screening process for directed conversion of active ingredients in a traditional Chinese medicine fermentation broth according to claim 3, characterized in that: Optimize the nitrogen source ratio and carbon-nitrogen balance equation: Among them C glucose =20g / L, C acetate =25g / L.

5. The strain screening process for directed conversion of active ingredients in traditional Chinese medicine fermentation broth according to claim 4, characterized in that: Also includes: The bacterial symbiotic synergistic effect model includes: Multi-species interaction gain coefficient ψ: k i is the active conversion efficiency of strain i; σ ij Competitive inhibitory factor.

6. The strain screening process for directed conversion of active ingredients in a traditional Chinese medicine fermentation broth according to claim 5, characterized in that: Also includes fermentation condition control parameters: Feedback control equation for dynamic regulation of temperature and pH: T(t)=T0+k p ·(pH target -pH(t)) T0=30℃,k p is the proportional gain coefficient.

7. The strain screening process for directed conversion of active ingredients in a traditional Chinese medicine fermentation broth according to claim 6, characterized in that: Also includes: Purity improvement process for target active ingredients, including: Calculation of the yield ζ in the separation and purification stage: r prod is the product formation rate, M pure The mass of the purified product.

8. The strain screening process for directed conversion of active ingredients in a traditional Chinese medicine fermentation broth according to claim 7, characterized in that: Also included are strain stability validation methods, including: Passage Adaptive Decay Model: λ is the decay constant, requiring the 10th generation 9. The strain screening process for directed conversion of active ingredients in a traditional Chinese medicine fermentation broth according to claim 8, characterized in that: Also includes: Chinese medicine substrate pretreatment process, The particle size distribution of raw materials meets the normal distribution where μ d =90 mesh, σ d ≤10 mesh; Relationship between enzymatic hydrolysis efficiency∈ and particle size: d is the particle diameter, d min =0.1mm.

10. The strain screening process for directed conversion of active ingredients in traditional Chinese medicine fermentation broth according to claim 9, characterized in that: Also includes product activity detection standards: HPLC was used to detect the content of target components, with a signal-to-noise ratio (SNR) ≥ 10:1; Microbial residue ≤10 2 CFU / mL, meeting: D value The sterilization time is decremented.

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