Protein-assembled high-strength multi-component millimeter sphere catalyst as well as preparation method and application thereof
The protein-assembly of millimeter-sized catalysts with a hydrophobic silica shell integrates enzymes and chemical catalysts within a macroscopic structure, addressing the challenge of integrating multiple components for continuous flow reactions with high strength and maintaining catalytic activity.
Patent Information
- Application Number
- CN202510441652.7
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- Filing Date
- 2025-04-09
- Publication Date
- 2025-07-15
AI Technical Summary
The prior art is difficult to assemble nanoparticles with various enzymes and chemical catalysts into macroscopic-sized particles with high strength, and it is difficult to achieve continuous reactions.
By encapsulating solid nanoparticles and proteins inside the hydrophobic silica shell, a millimeter spherical catalyst with a mechanical strength of 20 to 70N was formed. The nanoparticles were co-assembled with the enzyme by electrostatic action, hydrogen bonding and van der Waals forces to form a high-strength multicomponent millimeter spherical catalyst with a hierarchical pore structure.
The co-localization of different catalytic components in a single millimeter ball is achieved, the mechanical strength is enhanced, the catalytic activity is maintained, and the continuous flow catalytic reaction can be directly loaded into a fixed bed reactor, and the reaction conversion rate and enzyme activity are basically unchanged.
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Figure CN120310786A_ABST
Abstract
Description
Technical Field
[0001] The present invention belongs to the field of preparation of catalytic materials, and particularly relates to a high-strength multi-component millimeter sphere catalyst assembled by proteins, a preparation method thereof and an application thereof. Background Art
[0002] Assembling nanoparticles with catalytically active components such as chemical catalysts and enzymes in a spatially orthogonal manner into macroscopic-sized robust materials for continuous flow reactions is a cutting-edge technology with important practical application significance. Compared with micro-nano-sized catalysts, millimeter catalysts can be directly filled into the industrially preferred fixed-bed reactor for continuous flow reactions, and thus have received extensive attention from the academic and industrial communities. Although methods such as adsorption, encapsulation, and crosslinking have been successfully used for the immobilization of enzymes, these methods are not effective in the spatial orthogonal co-localization of multi-enzymes or even chemical catalysts. The key challenges come from two aspects: one is to firmly integrate different catalytic components and nanoparticles and further enable them to work synergistically. The other is to form multi-catalytic nanomaterials into macroscopic particles with sufficiently high mechanical strength and uniform morphology while still maintaining the initial catalytic activity / selectivity. Currently, through electrostatic, hydrogen bond, and van der Waals interactions between nanoparticles and enzymes, assembling nanoparticles and enzymes into nano-scale composite materials is expected to solve the above problems. However, various enzymes, coenzymes, and chemical catalysts cannot be assembled into macroscopic-sized materials with hierarchical pore structures and very low mechanical strength, making it difficult to achieve continuous reactions. Summary of the Invention
[0003] Aiming at the problem in the prior art that it is difficult to assemble nanoparticles with various enzymes and chemical catalysts into macroscopic-sized particles with high strength and use them for continuous flow reactions, the present invention provides a high-strength multi-component millimeter sphere catalyst assembled by proteins, a preparation method thereof and an application thereof. The catalyst has high strength and a millimeter size, and can be directly loaded into a fixed-bed reactor for continuous flow chemo-enzymatic tandem catalysis, enzymatic catalysis for preparing chiral amines, or multi-enzymatic tandem catalysis for preparing chiral amines.
[0004] To achieve the above object, the technical solution of the present invention is as follows:
[0005] On the one hand, the present invention provides a high-strength multi-component millimeter sphere catalyst assembled by proteins, which is mainly a millimeter sphere formed by encapsulating solid nanoparticles and proteins inside a hydrophobic silica shell layer. The particle size of the millimeter sphere is 1.0 - 5.0 mm, the protein content is 1 - 950 mg / g, and the mechanical strength is 20 - 70 N.
[0006] Further, the solid nanoparticles are any one or a mixture of mesoporous silica, solid silica spheres, or polystyrene spheres loaded with metals or immobilized enzymes, mesoporous alumina, polystyrene spheres, mesoporous silica, molecular sieves, carbon spheres, activated carbon, magnesium oxide, nano-hydroxyapatite, calcium oxide, solid alumina spheres, solid silica spheres, and hollow silica, etc., mixed in any ratio; the proteins are one or more of bovine serum albumin, horseradish peroxidase, transaminases ATA 101-ATA165 and their mutants, L-asparaginase, nicotinamide adenine dinucleotide phosphate, reduced nicotinamide adenine dinucleotide phosphate, pyridoxal 5'-phosphate, dextranase, luciferase, β-lactamase, carbonic anhydrase, alkene monooxygenase, lysozyme, trypsin, lipase, glucose oxidase, catalase, ketoreductase, formate dehydrogenase, alcohol dehydrogenase, formaldehyde dehydrogenase.
[0007] Furthermore, the metals include palladium, ruthenium, copper, zinc, iron, platinum, rhodium, nickel, copper, silver, and gold; the lipases include Candida antarctica lipase A, Candida antarctica lipase B, Penicillium camemberti lipase, Candida rugosa lipase, and Burkholderia cepacia lipase.
[0008] On the other hand, the present invention provides a method for preparing a high-strength multi-component millimeter ball catalyst assembled with the above-mentioned protein, comprising the following steps:
[0009] Step 1, adding the solid nanoparticles and the protein into water and magnetically stirring to obtain a mixed solution;
[0010] Step 2, continuously dropping the above mixed solution onto the hydrophobic silica powder spread on a flat surface to form droplet millimeter balls with a silica hydrophobic shell layer by rolling;
[0011] Step 3, collecting the droplet millimeter balls onto the substrate surface and slowly drying to obtain the high-strength multi-component millimeter ball catalyst assembled with the protein.
[0012] Further, the dosage ratio of the solid nanoparticles, the protein, and water in Step 1 is 0.1-0.5 g: 0.02-0.5 g: 1-3 mL.
[0013] Further, the hydrophobic silica powder in Step 2 is any one of Wacker H18 type hydrophobic fumed silica, Evonik Degussa R974 type, R972 type, R202 type, R812 type, R106 type, R8200 type hydrophobic fumed silica, and self-made hydrophobic mesoporous silica.
[0014] Further, the thickness of the hydrophobic silica powder in Step 2 is 1.0-3.0 mm.
[0015] Further, the substrate surface in step 3 is any one of a glass surface, a ceramic surface, a cardboard surface, a plastic surface, a wood board surface, and a metal surface.
[0016] Further, in step 3, the temperature for slow drying is 20-50 °C, and the time is 4-24 h.
[0017] On the other hand, the present invention also provides the application of the high-strength multi-component millimeter sphere catalyst assembled with proteins as described above, which is used for directly loading into a fixed-bed reactor for continuous flow catalytic reaction; the continuous flow tandem catalytic reaction includes chiral resolution transesterification reaction, chiral resolution acylation reaction, conversion of ketone to chiral amine, tandem conversion of alcohol to chiral amine, and metal-enzyme tandem reaction for synthesizing chiral (R)-1-phenylethyl 4-oxopentanoate derivative reaction.
[0018] Compared with the prior art, the beneficial effects of the present invention are as follows:
[0019] 1. The high-strength multi-component millimeter sphere catalyst assembled with proteins prepared by the present invention realizes that different enzymes and chemical catalysts can be co-localized in a single millimeter sphere in a spatially orthogonal manner, and can enhance the mechanical strength of the millimeter sphere; the enzymes inside the millimeter sphere can bond the nanoparticles together through electrostatic interaction, hydrogen bond and van der Waals force, enhancing the stability of the millimeter sphere skeleton structure, and obtaining a millimeter sphere catalyst with a mechanical strength as high as 20-70 N; the whole preparation process has mild conditions. During the assembly, the enzymes are integrated into the large pores of the millimeter sphere, while the chemical catalysts can be located in the small pores of the solid particles inside the millimeter sphere, avoiding direct contact with incompatible enzymes; this method can not only effectively enable different enzymes and chemical catalysts to be co-localized in a single millimeter sphere in a spatially orthogonal manner, but also ensure that the multi-active component millimeter sphere has high strength and participates in the tandem catalytic process;
[0020] 2. The high-strength multi-component millimeter sphere catalyst assembled with proteins prepared by the present invention is a microsphere with a millimeter-sized particle diameter, and can be directly filled into a fixed-bed reactor for continuous flow catalysis without post-treatment;
[0021] 3. The high-strength multi-component millimeter sphere catalyst assembled with proteins prepared by the present invention can be assembled into millimeter spheres by changing the composition of the suspension, such as two or more enzymes, coenzymes and chemical catalysts;
[0022] 4. The high-strength multi-component millimeter sphere catalyst assembled with proteins prepared by the present invention has a simple preparation method, mild conditions, does not affect the initial activity of the enzyme during the preparation process, does not affect the initial activity of the active sites on the solid nanoparticles during the immobilization process, and the active sites on the solid nanoparticles during the immobilization process will not be significantly lost;
[0023] 5. The high-strength multi-component millimeter sphere catalyst assembled by protein prepared in the present invention has a hydrophobic silica shell on its surface, which can effectively encapsulate the droplets dispersed with solid particles, effectively reduce the loss of enzymes and solid particles loaded with chemical catalysts, and is beneficial to the preparation of millimeter spheres on the surfaces of various substrates.
[0024] 6. The high-strength multi-component millimeter sphere catalyst assembled by protein prepared in the present invention can be directly loaded into a fixed-bed reactor for continuous chiral resolution transesterification reaction, chiral resolution acylation reaction, conversion of ketone to chiral amine, tandem conversion of alcohol to chiral amine, and reaction of synthesizing chiral (R)-1-phenylethyl 4-oxopentanoate derivatives by metal-enzyme tandem reaction. The continuous reaction can last for more than 1000 h, the reaction conversion rate remains basically unchanged, and the activity of the enzyme remains basically unchanged. BRIEF DESCRIPTION OF THE DRAWINGS
[0025] Figure 1 It is the particle size diagram and strength diagram of the high-strength multi-component millimeter sphere catalyst assembled by protein in Example 1 of the present invention;
[0026] Figure 2 It is the scanning electron microscope diagram and transmission electron microscope diagram of the internal structure of the high-strength multi-component millimeter sphere catalyst assembled by protein in Example 1 of the present invention;
[0027] Figure 3 It is the particle size diagram and strength diagram of the high-strength multi-component millimeter sphere catalyst assembled by protein in Example 2 of the present invention;
[0028] Figure 4 It is the scanning electron microscope diagram and strength diagram of the high-strength multi-component millimeter sphere catalyst assembled by protein in Example 3 of the present invention;
[0029] Figure 5 It is the particle size and scanning electron microscope diagram of the internal structure of the high-strength multi-component millimeter sphere catalyst assembled by protein in Example 4 of the present invention.
[0030] Figure 6 It is the particle size and scanning electron microscope diagram of the internal structure of the high-strength multi-component millimeter sphere catalyst assembled by protein in Example 5 of the present invention.
[0031] Figure 7 It is the reaction result diagram of the high-strength multi-component millimeter sphere catalyst assembled by protein in Example 6 of the present invention; DETAILED DESCRIPTION OF THE INVENTION
[0032] To facilitate the understanding of the present invention, the present invention will be described more comprehensively below. However, the present invention can be implemented in many different forms and is not limited to the embodiments described herein. On the contrary, these embodiments are provided to make the understanding of the disclosure of the present invention more thorough and comprehensive.
[0033] Example 1
[0034] A preparation method of a high-strength multi-component millimeter sphere catalyst for protein assembly, comprising the following steps:
[0035] (1) Weigh 0.4 g of mesoporous silica nanoparticles and 0.08 g of bovine serum albumin, add them to 1.52 mL of water, and prepare a mixed solution after stirring evenly.
[0036] (2) Add the mixed solution into a syringe with a needle inner diameter of 1.0 mm, and continuously drop the mixed solution onto the powder of R974 type hydrophobic silica with a thickness of 3.0 mm laid flat on the surface of a glass petri dish at a flow rate of 0.5 mL / min through an injection pump. The droplets slowly roll under the action of a shaker to form droplet millimeter spheres with a silica hydrophobic shell.
[0037] (3) Collect the droplet millimeter spheres onto a glass petri dish, and then place them in a constant temperature shaker to slowly dry them during the rolling process. The drying temperature is controlled at 20 °C; during the drying process, the protein in the droplets can bond the nanoparticles together through electrostatic interaction, hydrogen bond, and van der Waals force to achieve the co-assembly of enzymes and solid nanoparticles. The droplets gradually shrink, and the mechanical strength gradually increases. After 12 h, millimeter spheres with a mechanical strength of 40 N are obtained. Figure 1 is the particle size diagram of the prepared millimeter spheres. It can be seen from the figure that millimeter spheres with a size of about 2 mm are prepared. Figure 2 are the scanning electron microscope image and transmission electron microscope image of the internal structure of the prepared millimeter spheres. It can be seen from the figure that the inside of the prepared millimeter spheres is formed by the accumulation of silica with a size of about 30 nm. Solid nanoparticles and bovine serum albumin are evenly distributed in the millimeter spheres, and bovine serum albumin is on the outer surface of the solid nanoparticles.
[0038] Example 2
[0039] A preparation method of a high-strength multi-component millimeter sphere catalyst for protein assembly, comprising the following steps:
[0040] (1) Weigh 0.25 g of nano-hydroxyapatite nanoparticles and 0.15 g of catalase, add them to 1.6 mL of water, and prepare a mixed solution after stirring evenly.
[0041] (2) Add the mixed solution into a syringe with a needle inner diameter of 1 mm, and continuously drop the mixed solution onto the powder of R812 type hydrophobic silica with a thickness of 3.0 mm laid flat on the surface of copperplate paper at a flow rate of 0.5 mL / min through an injection pump. The droplets slowly roll under the action of a shaker to form droplet millimeter spheres with a silica hydrophobic shell.
[0042] (3) Collect the droplet millimeter balls onto a flat-bottomed ceramic evaporating dish, and then place it in a constant-temperature shaker to slowly dry during the rolling process, with the drying temperature controlled at 25 °C; during the drying process, the protein inside the droplet can bind the nanoparticles together through electrostatic interactions, hydrogen bonds, and van der Waals forces to achieve the co-assembly of the enzyme and solid nanoparticles. The droplet gradually shrinks and the mechanical strength gradually increases. After 18 h, millimeter balls with a mechanical strength of 32 N are obtained. Figure 3 The particle size diagram and strength diagram of the prepared millimeter balls are shown. It can be seen from the figure that millimeter balls with a size of about 2 mm are prepared.
[0043] Example 3
[0044] A preparation method of a high-strength multi-component millimeter ball catalyst assembled by protein includes the following steps:
[0045] (1) Weigh 0.3 g of solid spherical silica nanoparticles and 0.1 g of Candida antarctica lipase B, add them to 1.6 mL of water, and stir evenly to obtain a mixed solution.
[0046] (2) Add the mixed solution into a syringe with a needle inner diameter of 2 mm, and continuously drop the mixed solution onto the powder of H18-type hydrophobic silica with a thickness of 3.0 mm spread on the surface of a flat-bottomed ceramic evaporating dish at a flow rate of 0.8 mL / min through an injection pump. The droplets slowly roll under the action of the shaker to form droplet millimeter balls with a silica hydrophobic shell.
[0047] (3) Collect the droplet millimeter balls onto a flat-bottomed ceramic evaporating dish, and then place it in a constant-temperature shaker to slowly dry during the rolling process, with the drying temperature controlled at 25 °C; during the drying process, the protein inside the droplet can bind the nanoparticles together through electrostatic interactions, hydrogen bonds, and van der Waals forces to achieve the co-assembly of the enzyme and solid nanoparticles. The droplet gradually shrinks and the mechanical strength gradually increases. After 18 h, millimeter balls with a mechanical strength of 29 N are obtained. Figure 4 The scanning electron microscope image and strength diagram of the prepared millimeter balls are shown. It can be seen from the figure that millimeter balls with a size of about 2 mm are prepared.
[0048] Example 4
[0049] A preparation method of a high-strength multi-component millimeter ball catalyst assembled by protein includes the following steps:
[0050] (1) Weigh 0.25 g of palladium-loaded silica nanoparticles and 0.1 g of Candida antarctica lipase B, add them to 1.8 mL of water, and stir evenly to obtain a mixed solution.
[0051] (2) Add the mixed solution into a syringe with a needle inner diameter of 1.2 mm. Through an injection pump, continuously drip the mixed solution onto the powder of R972 type hydrophobic silica with a thickness of 2.0 mm laid flat on the surface of a polytetrafluoroethylene evaporating dish at a flow rate of 0.5 mL / min. The droplets slowly roll under the action of a shaker to form droplet millimeter balls with a hydrophobic silica shell.
[0052] (3) Collect the droplet millimeter balls onto the polytetrafluoroethylene evaporating dish, and then place them in a constant temperature shaker to slowly dry them during the rolling process. Control the drying temperature at 30 °C; during the drying process, the enzymes inside the droplets can bond the nanoparticles together through electrostatic interactions, hydrogen bonds, and van der Waals forces to achieve the co-assembly of enzymes and solid nanoparticles. The droplets gradually shrink and the mechanical strength gradually increases. After 10 h, millimeter balls with a mechanical strength of 26 N are obtained. Figure 5 Scanning electron micrographs of the particle size and internal structure of the prepared millimeter balls.
[0053] Example 5
[0054] A preparation method of a high-strength multi-component millimeter ball catalyst for protein assembly, comprising the following steps:
[0055] (1) Weigh 0.3 g of mesoporous silica nanoparticles, 0.07 g of transaminase ATA101, 0.07 g of ketoreductase, 0.02 g of nicotinamide adenine dinucleotide phosphate, and pyridoxal 5'-phosphate, add them to 2.3 mL of water, and stir evenly to obtain a mixed solution.
[0056] (2) Add the mixed solution into a syringe with a needle inner diameter of 1.5 mm. Through an injection pump, continuously drip the mixed solution onto the powder of R202 type hydrophobic silica with a thickness of 3.0 mm laid flat on a flat-bottomed stainless steel disc at a flow rate of 0.6 mL / min. The droplets slowly roll under the action of a shaker to form droplet millimeter balls with a hydrophobic silica shell.
[0057] (3) Collect the droplet millimeter balls onto the stainless steel disc, and then place them in a constant temperature shaker to slowly dry them during the rolling process. Control the drying temperature at 40 °C; during the drying process, the proteins inside the droplets can bond the nanoparticles together through electrostatic interactions, hydrogen bonds, and van der Waals forces to achieve the co-assembly of enzymes and solid nanoparticles. The droplets gradually shrink and the mechanical strength gradually increases. After 6 h, millimeter balls with a mechanical strength of 32 N are obtained. Figure 6 Scanning electron micrographs of the particle size and internal structure of the prepared millimeter balls.
[0058] Example 6
[0059] 1.5 g of the millimeter ball catalyst prepared in Example 3 was directly loaded into a fixed-bed reactor with an inner diameter of 1.34 cm. The reactor temperature was set at 55 °C, and a toluene solution of 1-phenylethylamine with a concentration of 0.5 mol / L and ethyl methoxyacetate with a concentration of 1.5 mol / L was fed into the reactor through a constant flow pump at a flow rate of 1.2 mL / h for reaction. The reaction was continuously carried out for 160 h, and the ee value of the chiral amide was greater than 99%, and the ee value of the chiral amine was greater than 99%. Figure 7 It is a reaction result diagram.
[0060] Example 7
[0061] 1.5 g of the millimeter ball catalyst prepared in Example 4 was directly loaded into a fixed-bed reactor with an inner diameter of 1.34 cm. The reactor temperature was set at 60 °C, and a toluene solution of 1-phenylethanol with a concentration of 0.1 mol / L, 4-pentynoic acid with a concentration of 0.23 mol / L, triethylamine with a concentration of 0.075 mol / L, and 1,3,5-trimethoxybenzene (internal standard) with a concentration of 0.1 mol / L was fed into the reactor through a constant flow pump at a flow rate of 0.9 mL / h for reaction. The reaction was continuously carried out for 1000 h, and the yield of (R)-1-phenethyl 4-oxopentanoate was greater than 47%, and the ee value was greater than 99%.
[0062] Example 8
[0063] 2.1 g of the millimeter ball catalyst prepared in Example 5 was directly loaded into a fixed-bed reactor with an inner diameter of 1.34 cm. The reactor temperature was set at 30 °C, and a toluene solution of (R)-1-phenylethylamine with a concentration of 0.1 mol / L, 1-(3-nitrophenyl)ethanol with a concentration of 0.05 mol / L, 94.5 mg of aldehyde-ketone reductase, 0.13 μmol of NADP + , 129.6 mg of transaminase, and 299 μmol of pyridoxal phosphate was fed into the reactor through a constant flow pump at a flow rate of 0.6 mL / h for reaction. The reaction was continuously carried out for 150 h, and the yield of (R)-1-(3-nitrophenyl)ethylamine was greater than 43%, and the conversion rate was greater than 49%.
[0064] The above are only examples for better explaining the present invention, and are not intended to limit it. Any modification or equivalent replacement that does not depart from the spirit and scope of the present invention falls within the scope covered by the present invention.
Claims
1. A high-strength multi-component millimeter sphere catalyst for protein assembly, characterized in that, The catalyst is mainly a millimeter sphere formed by encapsulating solid nanoparticles and proteins inside a hydrophobic silica shell. The millimeter sphere has a particle size of 1.0 - 5.0 mm, a protein content of 1 - 950 mg / g, and a mechanical strength of 20 - 70 N.
2. The preparation method of the high-strength multi-component millimeter sphere catalyst assembled by protein according to claim 1, characterized in that, The solid nanoparticles are any one or a mixture of any ratio of mesoporous silica or solid sphere silica or polystyrene spheres, mesoporous alumina, polystyrene spheres, mesoporous silica, molecular sieves, carbon spheres, activated carbon, magnesium oxide, nano-hydroxyapatite, calcium oxide, solid sphere alumina, solid sphere silica, and hollow silica loaded with metals or immobilized enzymes; the proteins are one or more of bovine serum albumin, horseradish peroxidase, transaminases ATA 101 - ATA 165 and their mutants, L-asparaginase, nicotinamide adenine dinucleotide phosphate, reduced nicotinamide adenine dinucleotide phosphate, pyridoxal 5'-phosphate, dextranase, luciferase, β-lactamase, carbonic anhydrase, alkene monooxygenase, lysozyme, trypsin, lipase, glucose oxidase, catalase, ketoreductase, formate dehydrogenase, alcohol dehydrogenase, and formaldehyde dehydrogenase.
3. The preparation method of the high-strength multi-component millimeter sphere catalyst assembled by proteins according to claim 2, wherein, The metals include palladium, ruthenium, copper, zinc, iron, platinum, rhodium, nickel, copper, silver, and gold; the lipases include Candida antarctica lipase A, Candida antarctica lipase B, Penicillium camemberti lipase, Candida rugosa lipase, and Burkholderia cepacia lipase.
4. The preparation method of the high-strength multi-component millimeter ball catalyst assembled by protein according to any one of claims 1 to 3, characterized in that, It includes the following steps: Step 1, adding the solid nanoparticles and proteins into water and magnetically stirring to obtain a mixed solution; Step 2, continuously dropping the above mixed solution onto hydrophobic silica powder spread on a flat surface and rolling to form millimeter liquid droplets with a hydrophobic silica shell; Step 3, collecting the millimeter liquid droplets on the substrate surface and slowly drying to obtain the high-strength multi-component millimeter sphere catalyst assembled with proteins.
5. The preparation method of the high-strength multi-component millimeter sphere catalyst assembled by proteins according to claim 4, characterized in that, In Step 1, the dosage ratio of the solid nanoparticles, proteins, and water is 0.1 - 0.5 g:0.02 - 0.5 g:1 - 3 mL.
6. The preparation method of the high-strength multi-component millimeter sphere catalyst assembled by protein according to claim 4, wherein, In Step 2, the hydrophobic silica powder is any one of Wacker H18 type hydrophobic fumed silica, Evonik Degussa R974 type, R972 type, R202 type, R812 type, R106 type, R8200 type hydrophobic fumed silica, and self-made hydrophobic mesoporous silica.
7. The preparation method of the high-strength multi-component millimeter sphere catalyst assembled by proteins according to claim 4, characterized in that, In Step 2, the thickness of the hydrophobic silica powder is 1.0 - 3.0 mm.
8. The preparation method of the high-strength multi-component millimeter sphere catalyst assembled by proteins according to claim 4, characterized in that, In Step 3, the substrate surface is any one of a glass surface, a ceramic surface, a cardboard surface, a plastic surface, a wooden board surface, and a metal surface.
9. The preparation method of the high-strength multi-component millimeter sphere catalyst assembled by proteins according to claim 4, characterized in that, In Step 3, the temperature for slow drying is 20 - 50 °C, and the time is 4 - 24 h.
10. Use of the high-strength multi-component millimeter sphere catalyst assembled by proteins according to any one of claims 1 to 3, characterized in that, It is used for directly loading into a fixed-bed reactor for continuous flow catalytic reactions; the continuous flow tandem catalytic reactions include chiral resolution transesterification reactions, chiral resolution acylation reactions, conversion of ketones to chiral amines, tandem conversion of alcohols to chiral amines, and metal-enzyme tandem reaction for synthesizing chiral (R)-1-phenylethyl 4-oxopentanoate derivatives reactions.