BIOTECHNOLOGY - V. H. Gerasymenko - 2006

Part II. Applied Biotechnologies

CHAPTER 11. BIOTECHNOLOGY OF ANTIBIOTIC PRODUCTION

11.2. MODIFICATION OF β-LACTAM ANTIBIOTICS

Over several decades of clinical antibiotic use, A large number of pathogenic microorganisms have emerged that have acquired hereditary resistance to drugs that were previously lethal to them. A way out of this critical situation was found through the chemical and enzymatic transformation of natural Antibiotics.

This has led to The Development of so-called semisynthetic antibiotics, whose structures incorporate minor modifications that do not affect the core atomic group responsible for the antibiotic effect. Specifically, natural Penicillins and Cephalosporins were modified using the immobilized enzyme penicillin amidase.

The synthesis of novel, more potent penicillin analogs relies on altering its side chain while preserving the integrity of the remaining Structure—the so-called antibiotic "core," 6-aminopenicillanic acid.

This breakthrough enabled the large-scale production of acid-stable Semisynthetic penicillins characterized by high efficacy against a broad spectrum of microbes, low toxicity, and resistance to the enzyme β-lactamase, which hydrolyzes the lactam ring and leads to a complete loss of antibiotic activity. The latter property is crucial, as many microorganisms producing β-lactamase are resistant to benzylpenicillin and several other penicillins.