How antibiotic Penicillin came in existence? Describe steps of commercial production of Penicillin.
Answers
THE STORY OF PENICILLIN:
In 1928 ,penicillin, the first true antibiotic, was discovered by Alexander Fleming, Professor of Bacteriology at St. Mary's Hospital in London.
Returning from holiday on September 3, 1928, Fleming began to sort through petri dishes containing colonies of Staphylococcus, bacteria that cause boils, sore throats and abscesses. He noticed something unusual on one dish. It was dotted with colonies, save for one area where a blob of mold was growing. The zone immediately around the mold—later identified as a rare strain of Penicillium notatum—was clear, as if the mold had secreted something that inhibited bacterial growth. This had happened to many other scientists, but they disregarded this phenomenon as the destruction of their cultures and discarded them.
Fleming , on the other hand, studied this.He found that his "mold juice" was capable of killing a wide range of harmful bacteria, such as streptococcus, meningococcus and the diphtheria bacillus.It was thus a laboratory curiosity.
It was Howard Florey, Ernst Chain Boris and their colleagues at the Sir William Dunn School of Pathology at Oxford University who turned penicillin from a laboratory curiosity into a life-saving drug.The first subject for penicillin was Albert, a 40-yr old policeman who cut himself while shaving.He was recovering when penicillin was applied to him, but died of a relapse as their was a lack of penicillin.
PRODUCTION:
General:
Penicillin is a secondary metabolite of certain species of Penicillium and is produced when growth of the fungus is inhibited by stress. It is not produced during active growth. The Penicillium cells are grown using a technique called fed-batch culture, in which the cells are constantly subject to stress, which is required for induction of penicillin production. The available carbon sources are also important: glucose inhibits penicillin production, whereas lactose does not. The pH and the levels of nitrogen, lysine, phosphate, and oxygen of the batches must also be carefully controlled.The biotechnological method of directed evolution has been applied to produce by mutation a large number of Penicillium strains. These techniques include error-prone PCR, DNA shuffling, ITCHY, and strand-overlap PCR.
Specific:
Biosynthesis of penicillin G (benzylpenicillin):
- The first step is the condensation of three amino acids—L-α-aminoadipic acid, L-cysteine, L-valine into a tripeptide. Before condensing into the tripeptide, the amino acid L-valine must undergo epimerization to become D-valine.
- The second step in the biosynthesis of penicillin G is the oxidative conversion of linear ACV into the bicyclic intermediate isopenicillin N by isopenicillin N synthase (IPNS), which is encoded by the gene pcbC
- The final step is a transamidation by isopenicillin N N-acyltransferase, in which the α-aminoadipyl side-chain of isopenicillin N is removed and exchanged for a phenylacetyl side-chain. This reaction is encoded by the gene penDE, which is unique in the process of obtaining penicillins.
These are the steps involved....
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