Application of cloud point system two-phase distribution bioreactor in 6-APA preparation by hydrolyzing penicillin with enzyme

A cloud point system, 6-APA technology, applied in the biological field, can solve the problem of penicillin acylase stability reduction, etc., achieve the effect of high operating flexibility, cost reduction, and realization of recycling

Inactive Publication Date: 2007-03-14
YICHENG GOTO PHARMA
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  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

The main reason why it cannot be industrialized is that the stability of penicillin acylase in the water-organic solvent two-phase system is significantly reduced. Improving the stability of penicillin acylase in the water-organic solvent two-phase system

Method used

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  • Application of cloud point system two-phase distribution bioreactor in 6-APA preparation by hydrolyzing penicillin with enzyme
  • Application of cloud point system two-phase distribution bioreactor in 6-APA preparation by hydrolyzing penicillin with enzyme
  • Application of cloud point system two-phase distribution bioreactor in 6-APA preparation by hydrolyzing penicillin with enzyme

Examples

Experimental program
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Effect test

Embodiment

[0065] 1. Example of extraction and hydrolysis:

[0066] Mix the solution with penicillin concentration of 8g / 100ml according to the volume ratio of surfactant Tergitol TMN-3 and penicillin solution at 1:5, adjust the pH to below 2.5, and take out the coacervate phase after standing at room temperature for more than 1 hour. The immobilized enzyme is 0.8 ± 0.01g, 15ml of phosphate buffer solution with initial pH7.8, the volume ratio of coacervate phase and buffer solution is 1: 4, after reacting for 3 hours, the pH of the solution is stable at equilibrium value 6.3, The solution phase product 6-APA concentration (excluding the crystalline fraction) reached 114.1 mM, while the total 6-APA concentration including the crystalline fraction reached 138.2 mM. (This indicates that there is also a reaction crystallization process for 6-APA under high product concentration and high pH conditions)

[0067] 2. Example of extraction and hydrolysis:

[0068] Mix the penicillin concentrati...

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Abstract

The present invention discloses the application of cloud point system in enzymati hydrolysis of penicillin to prepare 6-amino cefo alkanoic acid. By means of two phase distributing bioreactor technology with cloud point system, penicillin acylating enzyme is used in enzymati hydrolysis of penicillin G to prepare semi-synthesized 6-amino cefo alkanoic acid as the key intermediate for beta-lactam antibiotic. The process has direct extraction of penicillin from the fermented liquid without need of penicillin crystallization, direct extraction of phenylacetic acid in hydrolysis without needing addition acid or alkali to control pH value, and less produced wastes.

Description

technical field [0001] The invention belongs to the field of biotechnology, and in particular relates to the application of a cloud point system in the preparation of 6-APA by enzymatically hydrolyzing penicillin in the field of industrial biocatalysis. Background technique [0002] Enzymatic hydrolysis of penicillin is shown in Formula 1. Enzymatic hydrolysis of penicillin (PG) to prepare 6-aminopenicillanic acid (6-APA) and produce by-product phenylacetic acid (PAA) is an important basis for the antibiotic industry. [0003] [0004] Formula 1 [0005] The penicillin hydrolysis process generally adopts enzyme conversion technology at home and abroad, and its basic process is shown in Figure 1 (Abian et al, Improving the industrial production of 6-APA: enzymehydrolysis of penicillin G in the presence of organic solvents.Biotechnol Prog, 2003 , 19:1639-1642). The current process adopts extraction and crystallization by repeatedly adjusting t...

Claims

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Application Information

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IPC IPC(8): C12P37/06
Inventor 包达吴海桥王志龙
Owner YICHENG GOTO PHARMA
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