BIOTECHNOLOGY - V. H. Gerasymenko - 2006

Part II. Special Biotechnologies

CHAPTER 11. BIOTECHNOLOGY OF ANTIBIOTIC PRODUCTION

11.3. DEVELOPMENT OF NEW BIOTECHNOLOGY FOR ANTIBIOTIC PRODUCTION AND APPLICATION

Modern biotechnology is rooted in the achievements of molecular biology, Molecular Genetics, and Introduction/32.html">Genetic Engineering. Today, promising directions are being developed based on the understanding of antibiotic Biosynthesis pathways or their specific key structures. Several approaches and strategies are envisaged for establishing advanced biotechnology for large-scale antibiotic production.

1. The genetic engineering approach involves constructing producer strains using E.coli Plasmids as vectors to create recombinant DNAs. These contain genes that control The biosynthesis of Enzymes catalyzing the rate-limiting steps of antibiotic biosynthesis.

2. Isolation of rate-limiting reactions, followed by the genetic engineering design of "bottleneck" genes and the generation of a corresponding producer strain capable of producing an adequate amount of the primary metabolite that previously limited The rate of antibiotic biosynthesis. Implementing this technique has successfully enhanced the productivity of the cephalosporin producer.

3. Introduction into the microorganism genome of Genetic information encoding an enzyme necessary for the Modification of the produced antibiotic, such as its methylation via methylases.

4. Utilization of strong Inducers of nucleic acid and enzyme-METABOLISM/35.html">Protein Biosynthesis to increase the concentration of primary metabolites from which Antibiotics are formed in the presence of appropriate enzymes.

5. Enhancement of producer productivity through The Use of specific enzymes that regulate the transition of the microbial culture from the trophophase to the idiophase, as well as suppress retro-inhibition processes.

6. Mutational biosynthesis (mutasynthesis). Through microbial mutagenesis, mutant strains are obtained in which The formation of specific fragments of the antibiotic molecule is blocked. In mutasynthesis, these mutant strains are utilized to complete the Synthesis of the antibiotic molecule. Consequently, modified or so-called hybrid antibiotics are produced.

7. A novel technology employing super-producer strains of antibiotics, featuring enhanced self-protection mechanisms of the producer against the antibiotic it synthesizes.

8. The USE OF IMMOBILIZED enzymes in antibiotic production that catalyze both Hydrolysis and synthesis reactions at certain stages of manufacturing novel Penicillins and Cephalosporins. A promising approach involves whole producer Cells immobilized on a polymer support, enabling the complete synthesis of antibiotic preparations.

9. A highly promising approach is the encapsulation of antibiotics, particularly their incorporation into Liposomes, which ensures targeted delivery of the drug to target Organs (diseased Tissues) and minimizes adverse side effects.

10. Instead of administering the antibiotic itself, its producer—acting as an antagonist to the pathogen—can be introduced into the Organism. This concept originates from the works of I. I. Mechnikov on suppressing putrefactive microflora in the human colon using lactic acid Bacteria.

For instance, Dental caries is promoted by the wild pathogenic strain of the bacterium Streptococcus mutans residing in the Oral Cavity. It secretes acids that destroy tooth enamel and dentin. A mutant strain of this bacterial species, engineered not to produce corrosive acids upon introduction into the oral cavity, displaces the wild pathogenic strain and secretes a protein product lethal to it (Yegorov N.S. et al., 1987).