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CN111004826A - Preparation method of galactooligosaccharide powder - Google Patents

Preparation method of galactooligosaccharide powder Download PDF

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Publication number
CN111004826A
CN111004826A CN201911115468.4A CN201911115468A CN111004826A CN 111004826 A CN111004826 A CN 111004826A CN 201911115468 A CN201911115468 A CN 201911115468A CN 111004826 A CN111004826 A CN 111004826A
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galactooligosaccharide
galactosidase
solution
immobilized
prepare
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宋建民
王德海
宛荣生
张琴
王颂
黄祥君
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Anhui Minzhen Biological Engineering Co ltd
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Anhui Minzhen Biological Engineering Co ltd
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    • C12N9/00Enzymes; Proenzymes; Compositions thereof; Processes for preparing, activating, inhibiting, separating or purifying enzymes
    • C12N9/14Hydrolases (3)
    • C12N9/24Hydrolases (3) acting on glycosyl compounds (3.2)
    • C12N9/2402Hydrolases (3) acting on glycosyl compounds (3.2) hydrolysing O- and S- glycosyl compounds (3.2.1)
    • C12N9/2468Hydrolases (3) acting on glycosyl compounds (3.2) hydrolysing O- and S- glycosyl compounds (3.2.1) acting on beta-galactose-glycoside bonds, e.g. carrageenases (3.2.1.83; 3.2.1.157); beta-agarase (3.2.1.81)
    • C12N9/2471Beta-galactosidase (3.2.1.23), i.e. exo-(1-->4)-beta-D-galactanase
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Abstract

The invention discloses a preparation method of galactooligosaccharide powder in the related technical field of saccharide preparation, which comprises the steps of preparing activated macroporous alkalescent acrylic acid anion exchange resin, preparing immobilized β -galactosidase, preparing immobilized β -galactosidase particles, preparing galactooligosaccharide clear solution, preparing galactooligosaccharide syrup and the like to finally obtain the galactooligosaccharide powder, wherein the method comprises the steps of hydrolyzing lactose by using extracellular β -galactosidase to improve the production efficiency and save energy, immobilizing β -galactosidase and then producing to facilitate subsequent separation and purification, adding saccharomyces cerevisiae in the latter half of lactose hydrolysis reaction to improve the content of galactose and improve the quality of products, and filtering and nano-filtering to remove macromolecules in galactooligosaccharide before concentrating the galactooligosaccharide solution to further improve the purity of the products.

Description

Preparation method of galactooligosaccharide powder
Technical Field
The invention relates to the technical field related to saccharide preparation, in particular to a preparation method of galactooligosaccharide powder.
Background
Galacto-oligosaccharide is one of the functional oligosaccharides which have been developed internationally at present, and is the only oligosaccharide in various functional oligosaccharide varieties which is derived from animal milk at present. The molecular structure is generally that 1-7 galactosyl groups are connected on galactose or glucose molecules.
The preparation method of the galactooligosaccharide mainly comprises five methods, namely extraction from natural raw materials, acid hydrolysis of natural polysaccharide, chemical synthesis, fermentation synthesis and enzymatic synthesis, wherein the enzymatic synthesis is a mainstream production method, lactose is used as a raw material in the enzymatic synthesis, the lactose is hydrolyzed by β -galactosidase to generate glucose and galactose, and then 1-4 galactose molecules are connected on a galactosyl group by β -galactosidase catalysis to obtain the galactooligosaccharide.
The strains used for producing β -galactosidase at present are microorganisms such as Kluyveromyces fragilis (Kluyveromyces fragilis), Aspergillus niger (Aspergillus niger) Aspergillus oryzae (Aspergillus oryzae), and Kluyveromyces lactis (Kluyveromyces lactis), wherein β -galactosidase produced by Kluyveromyces fragilis is intracellular enzyme, and β -galactosidase produced by lactic acid yeast, Aspergillus niger, Aspergillus oryzae, Rhizopus oryzae, and the like is extracellular enzyme.
However, lactose is a disaccharide formed by combining glucose and galactose, the formation of galactose is accompanied with the formation of glucose along with the hydrolysis of lactose, and the excessive glucose causes the proportion of synthesized galacto-oligosaccharide to fail to meet the standard. In addition, the purity of the enzymatically synthesized galactooligosaccharides is limited by the current separation and purification techniques.
Disclosure of Invention
Aiming at the technical problems of overhigh glucose content and limited purity in galactose in the prior art, the invention provides a preparation method of galactooligosaccharide powder.
In order to achieve the purpose, the technical scheme of the invention is as follows:
1. a preparation method of galactooligosaccharide powder comprises the following steps:
s1) stirring glutaraldehyde and macroporous weakly basic acrylic acid anion exchange resin for 6-12 h at 16-32 ℃ to prepare activated macroporous weakly basic acrylic acid anion exchange resin;
s2) stirring β -galactosidase solution and the activated macroporous weak base acrylic acid anion exchange resin prepared in S1 to react for 12-24 h at 16-32 ℃ to prepare immobilized β -galactosidase;
s3) crushing the immobilized β -galactosidase prepared in the step S2, adding the crushed immobilized β -galactosidase into a mixed solution with the pH of 5-7 and containing 1-5% by mass of calcium chloride and 0.15-0.30% by mass of chitosan, and stirring the mixed solution at 48-52 ℃ for 24-36 hours to prepare immobilized β -galactosidase particles;
s4) mixing the immobilized β -galactosidase particles prepared in the S3 with a lactose solution with the concentration of 200-500 g/L, stirring and reacting for 6-8 h at the temperature of 35-40 ℃, adding Saccharomyces cerevisiae (Saccharomyces cerevisiae) to continue reacting for 4-6 h, and consuming glucose in the Saccharomyces cerevisiae to prepare galactooligosaccharide clear liquid with the purity of more than 57%;
s5) filtering to remove macromolecular proteins in the galactooligosaccharide clear solution prepared in the S4, and performing nanofiltration by using an organic membrane with the membrane aperture of 200-1000 Da to prepare a galactooligosaccharide solution;
s6) concentrating the galactooligosaccharide solution prepared in S5 to prepare galactooligosaccharide syrup;
s7) slowly adding maltodextrin and/or starch to the galactooligosaccharide syrup prepared in S6 under stirring until the galactooligosaccharide syrup becomes powder, namely, the galactooligosaccharide powder.
Further, the β -galactosidase in S2 was subjected to salting out purification treatment before use.
Furthermore, the ratio of the β -galactosidase to the macroporous weakly basic acrylic acid anion exchange resin in S2 is 100-200U/g, namely the enzyme activity of the β -galactosidase contained in each gram of the macroporous weakly basic acrylic acid anion exchange resin is 100-200U.
Further, the concentration of the β -galactosidase solution added in the S2 is 0.4-2.0U/mL.
Further, the stirring reaction in S4 needs 4000-20000U of the immobilized β -galactosidase to transport lactose solution to the reactor for reaction per kilogram of lactose on a dry basis.
Further, in the concentration in S6, the galactooligosaccharide solution prepared in S5 is concentrated by a plate evaporator until the solid content is 70-75%, and the concentration is stopped.
The invention has the following advantages:
1. the β -galactosidase outside the cells is utilized to hydrolyze the lactose, so that the production efficiency is improved, and the energy is saved;
2.β -galactosidase is immobilized and then produced, so that subsequent β -galactosidase can be conveniently separated from the product;
3. adding Saccharomyces cerevisiae (Saccharomyces cerevisiae) in the latter half of lactose hydrolysis reaction, and selectively consuming glucose generated by lactose hydrolysis by using the characteristic that the Saccharomyces cerevisiae preferentially utilizes glucose as a carbon source, so as to improve the content of galactose and the quality of the product;
4. and (3) filtering and nano-filtering the galactooligosaccharide solution before concentration to remove macromolecules in the galactooligosaccharide, thereby further improving the purity of the product.
Detailed Description
The following further describes the embodiments of the present invention. It should be noted that the description of the embodiments is provided to help understanding of the present invention, but the present invention is not limited thereto. In addition, the technical features involved in the embodiments of the present invention described below may be combined with each other as long as they do not conflict with each other.
Example one
S1) stirring glutaraldehyde and macroporous weakly basic acrylic acid anion exchange resin for 6-12 h at 16-32 ℃ to prepare activated macroporous weakly basic acrylic acid anion exchange resin;
s2) mixing β -galactosidase solution with the concentration of 0.4U/mL with the activated macroporous weak base acrylic acid anion exchange resin prepared by S1 according to the proportion that the enzyme activity of β -galactosidase contained in each gram of macroporous weak base acrylic acid anion exchange resin is 100U, and then stirring and reacting for 12h at 16 ℃ to prepare immobilized β -galactosidase;
s3) pulverizing the immobilized β -galactosidase prepared in S2, adding the pulverized immobilized β -galactosidase into a mixed solution with the pH of 5 and containing 1% by mass of calcium chloride and 0.15% by mass of chitosan, and stirring the mixed solution at 48 ℃ for 24 hours to prepare immobilized β -galactosidase granules;
s4) mixing the immobilized β -galactosidase particles prepared in the S3 with a lactose solution with the concentration of 200g/L, conveying the lactose solution into a reactor according to the consumption of 4000U of immobilized β -galactosidase per kilogram of lactose on a dry basis, stirring and reacting for 6 hours at 35 ℃, adding saccharomyces cerevisiae, continuing to react for 4 hours according to the original conditions, and consuming glucose in the saccharomyces cerevisiae to prepare a galactooligosaccharide clear solution with the purity of 57%;
s5) filtering to remove macromolecular proteins in the galactooligosaccharide clear solution prepared by the S4, and performing nanofiltration by using an organic membrane with the membrane aperture of 200Da to prepare a galactooligosaccharide solution;
s6) concentrating the galacto-oligosaccharide solution prepared in S5 by a plate evaporator until the solid content is 70%, and stopping concentrating to prepare galacto-oligosaccharide syrup;
s7) slowly adding maltodextrin to the galactooligosaccharide syrup prepared in the S6 under the stirring state until the galactooligosaccharide syrup becomes powder, thus obtaining galactooligosaccharide powder, wherein the mass content of the galactooligosaccharide in the powder is 90% in total sugar (galactooligosaccharide, glucose and lactose) through HPLC detection.
Example two
S1) stirring glutaraldehyde and macroporous weakly basic acrylic acid anion exchange resin for 9h at 24 ℃ to prepare activated macroporous weakly basic acrylic acid anion exchange resin;
s2) mixing β -galactosidase solution with the concentration of 1.2U/mL with the activated macroporous weak base acrylic acid anion exchange resin prepared by S1 according to the proportion that the enzyme activity of β -galactosidase contained in each gram of macroporous weak base acrylic acid anion exchange resin is 150U, and then stirring and reacting for 18h at 20 ℃ to prepare immobilized β -galactosidase;
s3) pulverizing the immobilized β -galactosidase prepared in S2, adding the pulverized immobilized β -galactosidase into a mixed solution with the pH of 6 and containing 3% by mass of calcium chloride and 0.20% by mass of chitosan, and stirring the mixed solution at 50 ℃ for 30 hours to prepare immobilized β -galactosidase particles;
s4) mixing the immobilized β -galactosidase particles prepared in the S3 with a lactose solution with the concentration of 300g/L, conveying the lactose solution into a reactor according to the consumption of 10000U of immobilized β -galactosidase per kilogram of lactose on a dry basis, stirring and reacting for 7 hours at 37 ℃, adding saccharomyces cerevisiae, continuing to react for 5 hours according to the original conditions, and consuming glucose in the saccharomyces cerevisiae to prepare a galactooligosaccharide clear solution with the purity of 60%;
s5) filtering to remove macromolecular proteins in the galactooligosaccharide clear solution prepared by the S4, and performing nanofiltration by using an organic membrane with the membrane aperture of 600Da to prepare a galactooligosaccharide solution;
s6) concentrating the galactooligosaccharide solution prepared in S5 by a plate evaporator until the solid content is 73%, and stopping concentrating to prepare galactooligosaccharide syrup;
s7) slowly adding starch into the galactooligosaccharide syrup prepared in S6 under stirring until the galactooligosaccharide syrup becomes powder, thus obtaining galactooligosaccharide powder, wherein the mass content of the galactooligosaccharide in the powder is 92% in total sugar (galactooligosaccharide, glucose and lactose) through HPLC detection.
EXAMPLE III
S1) stirring glutaraldehyde and macroporous weakly basic acrylic acid anion exchange resin for 10h at 28 ℃ to prepare activated macroporous weakly basic acrylic acid anion exchange resin;
s2) mixing β -galactosidase solution with the concentration of 1.8U/mL with the activated macroporous weak base acrylic acid anion exchange resin prepared by S1 according to the proportion that the enzyme activity of β -galactosidase contained in each gram of macroporous weak base acrylic acid anion exchange resin is 180U, and then stirring and reacting for 20h at 28 ℃ to prepare immobilized β -galactosidase;
s3) pulverizing the immobilized β -galactosidase prepared in S2, adding the pulverized immobilized β -galactosidase into a mixed solution with pH of 6 and containing 4% by mass of calcium chloride and 0.25% by mass of chitosan, and stirring the mixed solution at 50 ℃ for 32 hours to prepare immobilized β -galactosidase particles;
s4) mixing the immobilized β -galactosidase particles prepared in the S3 with a lactose solution with the concentration of 400g/L, conveying the lactose solution into a reactor according to the dosage of immobilized β -galactosidase with the requirement of 16000U per kilogram of lactose on a dry basis, stirring and reacting for 7 hours at 39 ℃, adding saccharomyces cerevisiae, continuing to react for 5 hours according to the original conditions, and consuming glucose in the saccharomyces cerevisiae to prepare a galactooligosaccharide clear solution with the purity of 65%;
s5) filtering to remove macromolecular proteins in the galactooligosaccharide clear solution prepared from S4, and performing nanofiltration by using an organic membrane with the membrane aperture of 800Da to prepare a galactooligosaccharide solution;
s6) concentrating the galacto-oligosaccharide solution prepared in S5 by a plate evaporator until the solid content is 72%, and stopping concentrating to prepare galacto-oligosaccharide syrup;
s7) slowly adding maltodextrin and starch into the galactooligosaccharide syrup prepared in S6 under stirring until the galactooligosaccharide syrup becomes powder, thus obtaining galactooligosaccharide powder, wherein the mass content of the galactooligosaccharide in the powder is 91% in total sugar (galactooligosaccharide, glucose and lactose) through HPLC detection.
Example four
S1) stirring glutaraldehyde and macroporous weakly basic acrylic acid anion exchange resin for 12h at 32 ℃ to prepare activated macroporous weakly basic acrylic acid anion exchange resin;
s2) mixing β -galactosidase solution with the concentration of 2.0U/mL with the activated macroporous weak base acrylic acid anion exchange resin prepared by S1 according to the proportion that the enzyme activity of β -galactosidase contained in each gram of macroporous weak base acrylic acid anion exchange resin is 200U, and then stirring and reacting for 24h at 32 ℃ to prepare immobilized β -galactosidase;
s3) pulverizing the immobilized β -galactosidase prepared in S2, adding the pulverized immobilized β -galactosidase into a mixed solution with the pH of 7 and containing 5% by mass of calcium chloride and 0.30% by mass of chitosan, and stirring the mixed solution at 52 ℃ for 36 hours to prepare immobilized β -galactosidase granules;
s4) mixing the immobilized β -galactosidase particles prepared in the S3 with a lactose solution with the concentration of 500g/L, conveying the lactose solution into a reactor according to the dosage of 20000U immobilized β -galactosidase required by each kilogram of lactose on a dry basis, stirring and reacting for 8 hours at 40 ℃, adding saccharomyces cerevisiae, continuing to react for 6 hours according to the original conditions, and consuming glucose in the reaction to prepare galacto-oligosaccharide clear liquid with the purity of more than 67%;
s5) filtering to remove macromolecular proteins in the galactooligosaccharide clear solution prepared by the S4, and performing nanofiltration by using an organic membrane with the membrane aperture of 1000Da to prepare a galactooligosaccharide solution;
s6) concentrating the galacto-oligosaccharide solution prepared in S5 by a plate evaporator until the solid content is 75%, and stopping concentrating to prepare galacto-oligosaccharide syrup;
s7) slowly adding a mixture of maltodextrin and starch into the galactooligosaccharide syrup prepared in S6 under stirring until the galactooligosaccharide syrup becomes powder, thus obtaining galactooligosaccharide powder, wherein the mass content of the galactooligosaccharide in the powder is 93% in total sugar (galactooligosaccharide, glucose and lactose) through HPLC detection.
EXAMPLE five
On the basis of any of the first to fourth embodiments, β -galactosidase in S2 was purified by salting out before use, and other conditions were the same as those in the previous embodiment.
The embodiments of the present invention have been described in detail, but the present invention is not limited to the described embodiments. It will be apparent to those skilled in the art that various changes, modifications, substitutions and alterations can be made in the embodiments without departing from the principles and spirit of the invention, and these embodiments are within the scope of the invention.

Claims (6)

1. A preparation method of galactooligosaccharide powder is characterized in that: the method comprises the following steps:
s1) stirring glutaraldehyde and macroporous weakly basic acrylic acid anion exchange resin for 6-12 h at 16-32 ℃ to prepare activated macroporous weakly basic acrylic acid anion exchange resin;
s2) stirring β -galactosidase solution and the activated macroporous weak base acrylic acid anion exchange resin prepared in S1 to react for 12-24 h at 16-32 ℃ to prepare immobilized β -galactosidase;
s3) crushing the immobilized β -galactosidase prepared in the step S2, adding the crushed immobilized β -galactosidase into a mixed solution with the pH of 5-7 and containing 1-5% by mass of calcium chloride and 0.15-0.30% by mass of chitosan, and stirring the mixed solution at 48-52 ℃ for 24-36 hours to prepare immobilized β -galactosidase particles;
s4) mixing the immobilized β -galactosidase particles prepared in the S3 with a lactose solution with the concentration of 200-500 g/L, stirring and reacting for 6-8 h at the temperature of 35-40 ℃, adding saccharomyces cerevisiae, and continuing to react for 4-6 h to prepare galactooligosaccharide clear liquid with the purity of more than 57%;
s5) filtering to remove macromolecular proteins in the galactooligosaccharide clear solution prepared in the S4, and performing nanofiltration by using an organic membrane with the membrane aperture of 200-1000 Da to prepare a galactooligosaccharide solution;
s6) concentrating the galactooligosaccharide solution prepared in S5 to prepare galactooligosaccharide syrup;
s7) adding maltodextrin and/or starch to the galactooligosaccharide syrup prepared in S6 to obtain a galactooligosaccharide powder.
2. The method for preparing galactooligosaccharide powder of claim 1, wherein the β -galactosidase in S2 is purified by salting out before use.
3. The method for preparing galactooligosaccharide powder of claim 1, wherein the ratio of the β -galactosidase to the macroporous weakly basic acrylic acid anion exchange resin in S2 is 100-200U/g.
4. The method for preparing galactooligosaccharide powder according to any one of claims 1 to 3, wherein the concentration of the β -galactosidase solution added to S2 is 0.4 to 2.0U/mL.
5. The method for preparing galactooligosaccharide powder of claim 1, wherein the stirring reaction in S4 requires 4000-20000U of the immobilized β -galactosidase to transport lactose solution to a reactor for reaction per kg of lactose on a dry basis.
6. The method for preparing galactooligosaccharide powder according to claim 1, wherein: and in the S6, concentrating the galactooligosaccharide solution prepared in the S5 by using a plate evaporator until the solid content is 70-75%, and stopping concentrating.
CN201911115468.4A 2019-11-14 2019-11-14 Preparation method of galactooligosaccharide powder Withdrawn CN111004826A (en)

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Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN119242737A (en) * 2024-12-04 2025-01-03 浙江晟格生物科技有限公司 Preparation method of galacto-oligosaccharide

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN119242737A (en) * 2024-12-04 2025-01-03 浙江晟格生物科技有限公司 Preparation method of galacto-oligosaccharide
CN119242737B (en) * 2024-12-04 2025-09-19 浙江晟格生物科技有限公司 Preparation method of galacto-oligosaccharide

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