Penicillin

= Penicillin =

General information

 * ~ Product Name || Penicillin ||
 * ~ Inventors || Sir Alexander Fleming (Discovery); Howard Florey and Ernst Chain (Isolation) ||
 * ~ Patent holders || No current patents ||
 * ~ Area of Application || Medicin, namely in infection treatment ||
 * ~ Market Size || Production of 20000 ton/year and market value of 600 million € ||

Penicillin was the first known antibiotic and it allowed to treat various diseases anda consequently to augment the average life expectancy. It's a natural antibiotic obteained by fermentation with the fungus //Penicillum c////hrysogenum// and it still has nowadys an important market value.

History
The discovery of Penicillin was one of the major breakthroughs of the XX century. It was the first known antibiotic and it had the most importance in the evolution of medicine: deathly diseases turned into curable diseases and the average life expectancy augmented. Penicillin was discovered in 1928 by Sir Alexander Fleming, some people say by accident. Though, Penicillin was only obtained in its purified form in 1940 by Howard Florey and Ernst Chain, from Oxford University. The strategic importance of Penicillin in World War II put Florey and Chain in German arrest warrants, so they had to move to United States in order to continue their research. For the discovery and isolation of Penicillin these three scientists were laureate with the Nobel Prize in Medicine in 1945.

Several Penicillins and derivatives: Structure, Market Value and Applications
Nowadays there are several Penicillins known and also a variety of Penicillin derivatives. All Penicillins share part of their structure: they have a common “nucleus”, the 6-aminopenicillanic acid (6-APA) constituted by a β-lactam and a tiazolidinic ring. It’s the side chain that differs from penicillin to penicillin depending on which radical is boundd to that site. The Penicillins with more industrial and economic interest are Penicillin G (benzilpenicillin) and Penicillin V (fenoximethylpenicillin) with a production and market value of 20000 ton/year and 600 million €. To treat a patient against bacterial infections the typical dosage  is 1 to 10 g of penicillin. This means that the world annual production of penicillin is enough to treat up to 20000 million patients, surpassing in a large scale the need of these antibiotics. The main  penicillin derivatives are semi-synthetic penicillins such as ampicillin and amoxicillin and also desacetoxicephalosporins, also known as oral cephalosporins. These compounds can be obtained through a series of chemical reactions. Their main application is as wide spectrum antibiotics that act on a much varied range of microorganisms and under more restricted conditions than regular penicillins.



Mechanism of Action
Penicillin prevents the growth of microorganisms by inhibiting with the formation of the peptidoglycan cross-link in bacteria cell wall. The β-lactam ring binds to the enzyme responsible for the linkage of the peptidoglycan molecules, weakening the cell wall and causing cytolysis due to increased osmotic pressure. In addition, the build-up of peptidoglycan precursors sets the activation of cell wall hydrolases that digest the existing peptidoglycan.

Industrial Production
Industrially, to produce penicillin the only method available is fermentation with the fungus //Penicillium chrysogenum// followed by the extraction of penicillin from the fermentative broth. There aren’t any alternative chemical ways to produce penicillin that are both effective and economically viable. The production occurs in agitated reactors with aeration, in fed-batch conditions which allows a better control of the conditions of the fermentation medium and to keep them in a pseudo-stationary state while the culture is kept in a transient state. The isolation of the penicillin produced during the fermentation is made in two steps: an extraction followed by crystallization. The extraction of the penicillin from the fermentative broth resorts to the use of a rich solvent (usually butyl acetate) from which the antibiotic is later isolated. The extraction is most commonly made in Podbielniak extractors although it can be made in other types of extractors. The final step in the crystallization of the penicillin from which results the antibiotic that can be submitted to other operations to change the final appearence.