Penicillin was discovered in 1928 by Alexander Fleming and revolutionized medicine by providing the first effective treatment for bacterial infections. It works by inhibiting the formation of bacterial cell walls, causing the cells to burst. Industrially, penicillin is produced through the fermentation of Penicillium chrysogenum fungus, which requires sugars, nitrogen sources, and other minerals. The downstream process involves removing cells through filtration and centrifugation, then purifying and assaying the penicillin.

1. Aum Sri Sai Ram
Production of Penicillin By-
Amit K Sahoo
15151

3. 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.

4. 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.

5. 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.

8. 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.

9. Contd..
• 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.

17. 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.

18. • 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.

19. INDUSTRIAL PRODUCTION OF
ANTIBIOTIC- PENICILLIN
• The industrial production of penicillin was broadly
classified in to two processes namely,
• Upstream processing
• Downstream processing

20. UPSTREAM PROCESSING
INOCULUM 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

21. UPSTREAM PROCESSING
• Upstream processing encompasses any technology
that leads to the synthesis of a product.
• Upstream includes the exploration, development and
production.

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

23. 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.

24. 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.

25. 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

26. 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

27. Fermenter

30. The main stages of Penicillin
production are:

31. Isolation and purification

32. Contd…

33. Assay for standardization

34. Contd…

35. References
• https://en.wikipedia.org/wiki/Penicillin
• https://www.drugs.com › Drugs A to Z
• www.healthline.com/drugs/penicillin-v/oral-tablet
• https://www.britannica.com/science/penicillin