Penicillin Production

Aum Sri Sai Ram

Production of Penicillin By-Amit K Sahoo15151

Penicillin

• Penicillin heralded the dawn of the antibiotic age. Before its introduction there was no effective treatment for infections such as pneumonia, gonorrhea or rheumatic fever. Hospitals were full of people with blood poisoning contracted from a cut or a scratch, and doctors could do little for them but wait and hope.

Alexander Fleming’s Discovery of Penicillin

• 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.

Contd…..

• Fleming found that his "mold juice" was capable of killing a wide range of harmful bacteria, such as streptococcus, meningococcus and the diphtheria bacillus. 

• In March 1942, Anne Miller became the first civilian to be treated successfully with penicillin having almost died from a huge infection following a miscarriage.

How penicillin works

• Penicillin works by indirectly bursting bacterial cell walls. It does this by acting directly on peptidoglycans, an important part of bacteria's structure.

• The peptidoglycan in bacteria's cell walls increases their strength and keeps external fluids and particles from entering them.

• Peptidoglycans form a mesh-like structure around the bacteria's plasma membrane.

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• When a bacterium multiplies, small holes open up in their cell walls as the cells divide. These holes are then backfilled with newly produced peptidoglycans, and the wall is reconstructed. That is unless penicillin is in the vicinity.

• Penicillin inhibit the protein struts that link the peptidoglycans together in the wall. This inhibition prevents the bacterium from closing the hole in its wall.

• Because of the difference in pressure between the inside of the bacterium and the surrounding fluid, water rushes into the hole and the bacterium bursts.

Antibiotic Production Methods

• Antibiotics are produced on an industrial scale using a variety of fungi and bacteria.

• Penicillin is produced by the fungus Penicillium chrysogenum which requires lactose, other sugars, and a source of nitrogen (in this case a yeast extract) in the medium to grow well.

• Like all antibiotics, penicillin is a secondary metabolite, so is only produced in the stationary phase.

• What sort of fermenter does it require?

It requires a batch fermenter, and a fed batch process is normally used to prolong the stationary period and so increase production.

INDUSTRIAL PRODUCTION OF ANTIBIOTIC- PENICILLIN

• The industrial production of penicillin was broadly classified in to two processes namely,

• Upstream processing • Downstream processing

UPSTREAM PROCESSINGINOCULUM PREPARATION• The medium is designed to provide the

organism with all the nutrients that it requires.

• Inoculation method- submerged technique

• Spores -major source of inoculum

UPSTREAM PROCESSING

• Upstream processing encompasses any technology that leads to the synthesis of a product.

• Upstream includes the exploration, development and production.

DOWNSTREAM PROCESSING

• The extraction and purification of a biotechnological product from fermentation is referred to as downstream processing.

STAGES IN DOWNSTREAM PROCESSING

Removal of cells

• The first step in product recovery is the separation of whole cells and other insoluble ingredients from the culture broth by technique such as filtration and centrifugation.

RAW MATERIALS• CARBON SOURCES:•

Lactose acts as a very satisfactory carbon compound, provided that is used in a concentration of 6%. Others such as glucose & sucrose may be used.

NITROGEN SOURCES:• Corn steep liquor (CSL)• Ammonium sulphate and ammonium

acetate can be used as nitrogenous sources.

Raw Materials Contd…

• MINERAL SOURCES:Elements namely potassium, phosphorus, magnesium, sulphur, zinc and copper are essential for penicillin production. Some of these are applied by corn steep liquor.

• Calcium can be added in the form of chalk to counter the natural acidity of CSL

• PAA- precursor

FERMENTATION PROCESS

• The medium is inoculated with a suspension of conidia of Penicillium chrysogenum.

• The medium is constantly aerated and agitated, and the mould grows throughout as pellets.

• After about seven days, growth is complete, the pH rises to 8.0 or above, and penicillin production ceases

Fermenter

The main stages of Penicillin production are:

Isolation and purification

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Assay for standardization

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References

• https://en.wikipedia.org/wiki/Penicillin• https://www.drugs.com › Drugs A to Z• www.healthline.com/drugs/penicillin-v/o

ral-tablet• https://

www.britannica.com/science/penicillin