阅读说明：本技术 一种酶法生产7-氨基头孢烷酸的方法 (Method for producing 7-aminocephalosporanic acid by enzyme method ) 是由 王辉 于 2020-04-23 设计创作，主要内容包括：本发明属于生物发酵工程技术领域,涉及一种酶法生产7-氨基头孢烷酸的方法。采用多段管道串联酶解。本发明在保证产品7ACA产量和纯度的前提下,酶用量只是现有工艺的1/2,不仅减小了工作难度,更是节约了生产成本。增加树脂对原料脱色除杂处理过程,树脂再生后可以重复使用,重复使用的效果好,原料脱色除杂效果好。(The invention belongs to the technical field of biological fermentation engineering, and relates to a method for producing 7-aminocephalosporanic acid by an enzyme method. And (3) performing enzymolysis by serially connecting a plurality of sections of pipelines. On the premise of ensuring the yield and purity of the 7ACA product, the invention only uses 1/2 of the prior art, thereby not only reducing the working difficulty, but also saving the production cost. The process of decoloring and impurity removing of the resin on the raw materials is added, the resin can be reused after regeneration, the effect of reuse is good, and the effect of decoloring and impurity removing of the raw materials is good.)

1. A method for producing 7-aminocephalosporanic acid by an enzyme method is characterized in that a plurality of sections of pipelines are connected in series for enzymolysis.

2. The enzymatic process for producing 7-aminocephalosporanic acid according to claim 1, characterized by comprising the steps of: adjusting the pH of cephalosporin C sodium salt to be neutral, decoloring and removing impurities, and then injecting into a series pipeline, wherein enzyme is added in advance in the pipeline; the PH value in the pipeline is 8.3-8.4.

3. The method for producing 7-aminocephalosporanic acid by the enzyme method according to claim 2, wherein the number of the enzymolysis pipelines is 5-15, and each group comprises at least one enzyme column containing acylase and an enzymolysis liquid temporary storage tank; and (3) eliminating an inlet end, connecting a new pipeline in which an enzyme is added in advance behind the last group of pipelines after the product detection reaches a set value, eliminating the first group of pipelines, and circulating the pipelines in sequence, wherein the temperatures in the enzyme column and the temporary storage tank of the enzymatic hydrolysate are 10-14 ℃.

4. The method for producing 7-aminocephalosporanic acid by the enzyme method according to claim 2, wherein a bactericide is added to the temporary storage tank of the enzymatic hydrolysate.

5. The method for producing 7-aminocephalosporanic acid by the enzyme method according to claim 2, wherein each section of the pipeline is provided with a PH meter and an alkali adding port.

6. The enzymatic process for producing 7-aminocephalosporanic acid according to claim 3, wherein the set value is a lower limit of a product concentration requirement.

7. The method for producing 7-aminocephalosporanic acid by the enzyme method according to claim 3, wherein the cephalosporin C sodium salt is used for decoloring and impurity removal after the PH is adjusted to be neutral by adopting a resin column, the resin column is fresh or regenerated for 1-20 times, and the regenerated resin is treated by adopting a mixed solution of 8% of NaCl and 2% of NaOH by mass fraction.

8. The enzymatic process for producing 7-aminocephalosporanic acid according to claim 7, wherein the resin column is suqing No. 3.

9. The method for producing 7-aminocephalosporanic acid by the enzymatic method according to claim 7, wherein the pH is adjusted by using a sodium bicarbonate aqueous solution with a mass fraction of 10% -15%.

Technical Field

The invention belongs to the technical field of biological fermentation engineering, and relates to a method for producing 7-aminocephalosporanic acid by an enzyme method.

Background

The existing method for producing 7-aminocephalosporanic acid is an enzymolysis method, and the traditional enzymolysis method is that a certain proportion of acylase is put into a manhole at the top of an enzymolysis tank, one bag of acylase is put into the enzymolysis tank, and the manhole is sealed after the enzyme is put into the tank. Then purified water is injected into the enzymolysis tank for 3-4 times, and the enzyme is cleaned for standby. In the production process, firstly, the cephaloc (cephalosporin C sodium salt) concentrated solution is heated in an adjusting tank to raise the temperature and adjust the pH value until the pH value meets the requirements of the production process, secondly, the prepared cephaloc concentrated solution is pumped into an enzymolysis tank by a pump to be fully stirred with 7ACA enzyme, the change of the pH value needs to be noticed all the time in the enzymolysis process, and after the cephaloc concentrated solution is completely enzymolyzed for one hour, qualified 7ACA feed liquid is transferred out. And injecting the concentrated solution of the first C into the adjusting tank again, and starting the next round of enzymolysis. As the number of enzymolysis rounds increases, the acylase is attenuated and inactivated, and at the moment, workers need to take the acylase out to replace the acylase with a new one. After the bacteria are infected, the enzyme activity is reduced. The enzymolysis time is also correspondingly prolonged, so that the production efficiency is reduced, and in order to ensure the production efficiency and the production progress, new enzyme has to be frequently replaced.

The current enzymolysis method mainly has the following problems:

(1) the heating and temperature rising of the concentrated solution of the head C are not easy to control, and the head C is easy to degrade under high temperature and high PH in the adjusting tank and is damaged due to bacteria breeding.

(2) The workload is large, the enzyme is required to be loaded and unloaded one by one from the manhole at the top end of the enzymolysis tank no matter the enzyme is put into or taken out, and the manhole is very troublesome to open or seal again each time.

(3) With the increase of the number of enzymolysis rounds, the reduction of the contamination and the enzyme activity of the enzyme can both prolong the enzymolysis time, and if the enzyme is not replaced in time, the production efficiency and the progress can be greatly influenced.

(4) The enzyme consumption is large, and the enzyme is replaced by new enzyme so as not to influence the production efficiency and progress, thereby greatly reducing the utilization rate of the acylase and increasing the production cost.

Disclosure of Invention

The invention provides a novel method for producing 7-aminocephalosporanic acid by an enzyme method aiming at the problems in the traditional enzymolysis.

In order to achieve the purpose, the invention is realized by adopting the following technical scheme:

a method for producing 7-aminocephalosporanic acid by an enzyme method adopts a plurality of sections of pipelines to be connected in series for enzymolysis.

Preferably, the method for producing 7-aminocephalosporanic acid by the enzymatic method comprises the following steps: adjusting the pH of cephalosporin C sodium salt to be neutral, decoloring and removing impurities, and then injecting into a series pipeline, wherein enzyme is added in advance in the pipeline; the pH value in the pipeline is adjusted to 8.3-8.4.

Preferably, the number of the enzymolysis pipelines is 5-15, and each group comprises at least one enzyme column filled with acylase and an enzymolysis liquid temporary storage tank; and (3) eliminating an inlet end, connecting a new pipeline in which an enzyme is added in advance behind the last group of pipelines after the product detection reaches a set value, eliminating the first group of pipelines, and circulating the pipelines in sequence, wherein the temperatures in the enzyme column and the temporary storage tank of the enzymatic hydrolysate are 10-14 ℃.

Preferably, a bactericide is added into the temporary storage tank of the enzymolysis liquid.

Preferably, each section of pipeline is provided with a PH meter and an alkali adding port.

Preferably, the set value is a product concentration requirement lower limit.

Preferably, the cephalosporin C sodium salt is used for decoloring and impurity removal after the pH is adjusted to be neutral by adopting a resin column, the resin column is fresh or regenerated for 1-20 times, and the regenerated resin is treated by adopting a mixed solution of 8% of NaCl and 2% of NaOH in mass fraction.

Preferably, the resin column is suqing No. 3.

Preferably, the pH is adjusted by using 10-15% of sodium bicarbonate aqueous solution by mass fraction.

Compared with the prior art, the invention has the advantages and positive effects that:

1. on the premise of ensuring the yield and purity of the 7ACA (7-aminocephalosporanic acid) product, the enzyme dosage is only 1/2 of the original process, so that the working difficulty is reduced, and the production cost is saved.

2. The process of decoloring and impurity removing of the resin on the raw materials is added, the resin can be reused after regeneration, the effect of reuse is good, and the effect of decoloring and impurity removing of the raw materials is good.

Detailed Description

In order that the above objects, features and advantages of the present invention may be more clearly understood, the present invention will be further described with reference to specific embodiments. It should be noted that the embodiments and features of the embodiments of the present application may be combined with each other without conflict.

In the following description, numerous specific details are set forth in order to provide a thorough understanding of the present invention, however, the present invention may be practiced in other ways than those specifically described herein, and thus the present invention is not limited to the specific embodiments of the present disclosure.