ECOLOGICAL BIOCHEMISTRY - Study Guide - V. M. Isaienko 2005

Chapter 11. ECOLOGICAL BIOCHEMISTRY AND BIOTECHNOLOGY

11.1. Biotechnology and Medicine

The advancements of biotechnology in medicine are primarily associated with large-scale research and its rapid practical Structure/175.html">Implementation. Medical Biotechnology likely originated with the onset of industrial penicillin production in the 1940s. The first penicillin-G (benzylpenicillin) acted predominantly against Gram-positive Bacteria (Fig. 11.1).

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Fig. 11.1. Structure of benzylpenicillin

During The production of benzylpenicillin, researchers significantly increased its yield by developing a series of mutants from the original Penicillium chrysogenum strain and altering cultivation conditions. Additionally, new Antibiotics active against Gram-negative bacteria were obtained: streptomycin, synthesized by bacteria of the genera Actinomycetes and Streptomycetes, and cephalosporin, produced by the mold fungus Cephalosporium. Ampicillin is a derivative of benzylpenicillin, differing only in the presence of an additional amino group in its side chain (Fig. 11.2).

Fig. 11.2. Structure of ampicillin

Ampicillin is active upon oral administration and targets a broad spectrum of bacteria, including certain Gram-negative strains that cause respiratory infections (Haemophilus influenzae), digestive disorders (Shigella and Salmonella), and Urinary Tract infections (Escherichia coli and Proteus). Cloxacillin is also acid-stable (Fig. 11.3).

Fig. 11.3. Structure of cloxacillin

It is frequently prescribed alongside ampicillin for patients diagnosed with Staphylococcal infections.

Another example of utilizing intact Cells with an unknown Gene for pharmaceutical production is the synthesis of interferon by cultivated lymphoblast cells. Interferons trigger antiviral responses, inhibit Cell proliferation, and modulate The Immune System.

Microorganisms are also employed in specific stages of drug synthesis. For instance, the bread mold strain Rhizopus arrhizus is capable of hydroxylating progesterone at the initial stage of synthesizing the steroid derivative cortisone.

Using Recombinant DNA technology, the human leukocyte interferon gene was successfully incorporated into a plasmid and cloned in Escherichia coli. The fibroblast interferon gene was introduced into the same bacterium. Furthermore, the expression of the human interferon gene was successfully achieved in Yeast cells.

Recombinant DNA technology has been successfully applied to Insulin production. In The First stage, the DNA sequence is reconstructed based on the Amino Acid Sequence of insulin by separately synthesizing the genes for its A- and B-chains. A Methionine codon is placed at the 5'-end of each chain, and termination sequences at the 3'-ends. Each gene is then inserted into the β-galactosidase gene of Plasmids, which are subsequently introduced into Escherichia coli cells. The bacteria are grown in a galactose-containing medium, which induces the synthesis of β-galactosidase, and along with it, the A- and B-chains of insulin attached via a methionine residue. Following bacterial lysis and Treatment with Cyanogen bromide—which specifically cleaves Proteins at the methionine residue—the insulin chains are separated from β-galactosidase. The chains are then subjected to oxidation and recombination, resulting in The formation of the double-chain insulin molecule.