Application of Enzyme Engineering Technology in Pharmaceutical Industry

The role of enzymes in the pharmaceutical industry is mainly to catalyze the conversion of precursor substances into drugs. In addition, immobilized enzyme membranes or enzyme tubes are also widely used in the parameter detection and measurement of pharmaceutical processes, especially biopharmaceutical processes. Several typical applications of enzyme engineering technology in pharmaceutical industry are described below as examples.

Penicillin acylase can use penicillin or cephalosporin as a raw material. It can catalyze the formation and cleavage of amido bonds at position 6 of penicillin or position 7 of cephalosporin. The typical application sequence is to first catalyze the cleavage of penicillin or cephalosporin amido linkages to obtain the direct substrate of semi-synthetic antibiotics, 6-aminopenicillin (6-APA) or 7-aminocephalosporin (7-ACA). ); Then catalyze the formation of new amido bonds in the presence of other acyl donors, thereby obtaining new antibiotics with entirely new side chains.

There are two types of penicillin produced by natural fermentation, one is penicillin G and the other is penicillin V. Many novel semi-synthetic penicillins can be obtained by carrying out acyl replacement reactions under the catalysis of penicillin acylase and replacing phenylacetyl with new acyl donors. For example, ampicillin can be obtained by replacing the original phenylacetyl with?aminophenylacetyl. Amoxicillin, carbenicillin, and sulfacillin are also obtained by the enzyme-catalyzed semi-synthesis method through the acyl substitution reaction of penicillin.

Cephamycin produced by natural fermentation is cephalosporin C. Cefomycin C is firstly hydrolyzed to 7-ACA under the catalysis of penicillin acylase, and then reacts with side chain carboxylic acid derivatives to form various new cephalosporins. For example: ceftizidine, cephalosporin, cephalexin and so on.

Although penicillin acylase can catalyze to form amido bonds, as well as its hydrolysis, it has the ability to catalyze both forward and reverse reactions. However, the conditions required for the catalytic hydrolysis reaction and the catalytic synthesis reaction are quite different, especially the optimal catalytic pH differs greatly. The pH of the commonly used catalytic hydrolysis reaction is 7.0-8.0, and the pH of the catalytic synthesis reaction should be lowered to 5.0-7.0. Therefore, two consecutive but independent reactors should be used for the hydrolysis and synthesis reactions.

Application of enzymes to biological macromolecules

Because Chinese herbal medicines are mostly derived from plants, that is, medicinal plants. But only some specific small molecule components in these plants are the medicinal components. Extraction of Chinese herbal medicine preparation is to extract these active ingredients from the whole plant or organ and combine them with auxiliary materials to prepare medicines suitable for storage, transportation and administration. The first step in this process is the crushing and extraction of Chinese herbal medicines. Due to the presence of cellulose in plants, the crushing of herbal medicines becomes more difficult. A feasible solution is to use cellulase to degrade cellulose to form soluble monosaccharides, thereby increasing its solubility and reducing viscosity. However, due to the high price of cellulases, this application is currently limited to laboratory research.

In addition, the use of cellulase to degrade cellulose in crop straw to form soluble monosaccharides that can be used by microorganisms can enable microorganisms in biomass energy systems to ferment using cellulose, which was previously difficult to use, as a carbon source, thereby improving productivity.

Application of immobilized enzymes in biosensors

Biosensor is an interdisciplinary organic combination of bioactive materials (enzymes, proteins, DNA, antibodies, antigens, biofilms, etc.) and physical and chemical transducers. It is an advanced detection method essential for the development of biotechnology. And the monitoring method is also a fast, trace analysis method at the molecular level.

In the development of knowledge economy in the 21st century, biosensor technology will be a new growth point between information and biotechnology. It has extensive application prospects in clinical diagnosis, industrial control, food and drug analysis, environmental protection, and biotechnology, biochip and other research in the national economy.

The principle is that the substance to be measured enters the bioactive material through diffusion and undergoes a biological reaction after molecular recognition, and the generated information is then converted into a quantifiable and processable electrical signal by the corresponding physical or chemical transducer. After two more times of instrument amplification and output, we can know the concentration of the analyte.

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