Antibiotics are among the most frequently prescribed medications in modern medicine. Antibiotics cure disease by killing bacteria and keeping them from reproducing. Penicillin was the first antibiotic, discovered accidentally from a mold culture. Presently, over 100 different antibiotics are available in the market to cure minor discomforts as well as lifethreatening infections. Antibiotics are very useful in a wide variety of infections, but they only treat bacterial infections. Antibiotics are useless against viral infections (for example, the common cold) and fungal infections (such as ringworm).
Penicillin is a group of antibiotics derived from Penicillium fungi. Penicillin is a historically significant drug being the first antibiotic discovered. Penicillin is a Betalactam antibiotic and is used in the treatment of bacterial infections caused by susceptible, usually Gram-positive, organisms. Figure1: Core structure of Penicillin: R-C9H11N2O4S
In September 1928, Alexander Fleming accidentally discovered penicillin when he was engaged in studying different kinds of bacteria and molds in his laboratory. He once opened one of his Petri dishes for a few seconds to smear it with a strain of staphylococcus which is a bacterium that typically occurs in clusters resembling grapes. Fleming noticed a halo of inhibition of bacterial growth around a contaminant blue-green mold staphylococcus plate culture. He concluded that the mold was releasing a substance that was inhibiting bacterial growth and lysing the bacteria. He grew a pure culture of the mold and discovered that it was a penisillium mold, now known to be penicillium notatum. He then demionstrated that this material had powerful antimicrobial properties and named the product penicillin. Fleming carefully preserved the culture, but the discovery lay essentially dormant for over a decade. World War 2 provided the impetus to resurrect the discovery. The development of penicillin for the medical use is attributed to an Australian nobleman called Howard Walter Florey who worked with a team at Oxford University. They wanted to investigate the biochemical and biological properties of antibacterial substances that microorganisms might possess. The team eventually discovered that penicillin was a molecule and not an enzyme as physicians used to consider it. The team also discovered that penicillin was very unstable unlike other simple molecules. Florey’s team members were able to produce stable penicillin by reducing the temperature of a water solution of penicillin by freeze drying it. Then, Florey experimented 1
penicillin on animals before he applied it on human beings. Penicillin was produced by a surface culture method early in World War II. Sub-merged culture methods were introduced by 1943 and are now almost exclusively employed.
Parameters that affect fermenetation:
Penicillin is a secondary metabolite of fungus Penicillium that is produced when growth of the fungus is inhibited by stress. It is not produced during active growth. Production is also limited by feedback in the synthesis pathway of penicillin. α-ketoglutarate + AcCoA → homocitrate → L-α-aminoadipic acid → L-Lysine + β-lactam The by-product L-Lysine inhibits the production of homocitrate, so the presence of exogenous lysine should be avoided in penicillin production. The Penicillium cells are grown using a technique called fed-batch culture, in which the cells are constantly subject to stress and will produce plenty of penicillin. The carbon sources that are available are also important: glucose inhibits penicillin, whereas lactose does not. Penicillin production needs strict asceptic conditions. Contamination by other microorganisms reduces the yield of penicillin. The pH and the levels of nitrogen, lysine, phosphate, and oxygen of the batches must be controlled. Temperature is an important factor affecting the performance of the cells. As the temperature is...