Introduction : Antibiotics are antimicrobial agents produced naturally by other microbes (usually fungi or bacteria) The first antibiotic was discovered in 1896 by Ernest Duchesne and in 1928 "rediscovered" by Alexander Fleming from the filamentous fungus Penicilium notatum. The antibiotic substance, named penicillin, was not purified until the 1940s (by Florey and Chain), just in time to be used at the end of the second world war. Penicillin was the first important commercial product produced by an aerobic, submerged fermentation

2. Presented By-
Nischitha R.
2st M.Sc., 3nd Semester.

3. CONTENTS• Introduction
• Properties of penicillin
• Types of penicillin
• Basic structure of penicillin
• Commercial production of penicillin
• Conclusion
• References

4. • Antibiotics are antimicrobial agents produced naturally by other
microbes (usually fungi or bacteria)
• The first antibiotic was discovered in 1896 by Ernest Duchesne and
in 1928 "rediscovered" by Alexander Fleming from the
filamentous fungus Penicilium notatum.
• The antibiotic substance, named penicillin, was not purified until
the 1940s (by Florey and Chain), just in time to be used at the end
of the second world war.
• Penicillin was the first important commercial product produced by
an aerobic, submerged fermentation
Introduction :
Cont..,

5. • Penicillin is produced by the fungus Penicilium 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.
Cont..,

6. • It exhibits the properties of a typical secondary metabolites.
• It active against certain Gram- positive bacteria in presence of
blood, pus and body fluids.
• It is soluble in water. It is very soluble in acetone, ethyl alcohol and
ether and it is less soluble in benzene, chloroform, ect..
• Aqueous solution of penicillin are unstable and must be stored
under refrigeration.
• Penicillin is most stable in the pᴴ range of 6.0 to 6.5 and
reasonably stable over the pᴴ range of 5.5 to 7.5 .
Properties of penicillin :

7. • Penicillin are compound of the general formula C₁₆H₁₈N₂O₅S –R, in
which R represents the radical or group that is different for each
day. The structural formula of the most common type ( F, G, X and
k ) are given.
• Penicillin F, G, X and K are produced by strain of the penicillin
notatum – chrysogenum group of molds ; flavicidin ( flavicin) by
Aspergilus flavus ; and dihydro F penicillin (gigantic acid ) by
Aspergilus gigantic.
• The basic structure of the penicillin's is 6- aminopenicillenic acid
(6- APA) , composed of a thiozolidine ring fused with a β- lactam
ring whose 6- amino position carries a variety of acyl substituent's.
Types of penicillin :
Basic structure of penicillin :

8. • The Inoculum : Master stock (spores) is the source of
inoculum. Spores (P. chrysogenum) from working stocks cultured
are suspended in water or non toxic lauryl sulphonate, then added
to the flask containing wheat bran and nutrient soln. A shake flask
culture of 4 day old is inoculated into a seed tank for 3 days.
• The medium : Jackson in 1958 prepared a media for penicillin
production . The major constituent of typical medium includes,
Commercial production of penicillin :
1) Fermentable carbohydrate
2) Potassium dihydrogen phosphate
3) Organic nitrogen source
4) Phenyl acetic acid precursor
5) Edible oil
6) Calcium carbonate (act as buffer)
7) Pᴴ after sterilization
Corn steep liquor(3.5%),
lactose(3.5%),glucose(1%).
0.4%
0.25%
1%
5.5% to 6.0% Cont..,

9. • Aeration (oxygen supply) : supply of oxygen in a bioreactor is
the limiting factor in penicillin biosynthesis. Aeration speed is
between 3.0 to 1.5 .
• Temperature : Temperature plays an important role in penicillin
production it should be mentioned at 28° C.
• Biomass production : production of penicillin depends upon
biomass production therefore, it is describle to have a high
biomass concentration in the vessel. It is achieved by increasing
the agitation rate and power.
• Pᴴ : It is maintained early neutrality by calcium and magnesium
carbonate in the medium by phosphate buffer. It is also controlled
by adding sodium hydroxide or sulphuric acid in the medium.
Cont..,

10. • Procedure :

11. Batch fermenter

12. • Recovery and purification : Harvested culture broth
includes penicillin G along with a variety of other metabolites .
Vacuum filter is used for separation of mycelium from the broth
on a rotary .conversion of penicillin to the anionic form occurs at
low pᴴ (2.0 to 2.5).the lowering of pᴴ is done by adding phosphoric
acid or sulphuric acid. For removal of pigment and other
impurities from solvent containing penicillin it is treated with
active charcoal. The product is back extracted into water from
solvent by adding potassium or sodium hydroxide to form its sail.
The product of penicillin is then crystallized into sodium or
potassium penicillin.

13. • Antibiotics are probably the most important group of
compounds synthesized by industrial microorganisms.
• The best known and probably the most medically important
antibiotics are the β- lactam, penicillin and cephalosporin's.
• Penicillin exhibits the properties of a typical secondary
metabolites.
• Penicillin is commercially produced usually via a fed batch
process carried out aseptically in stirred tank fermenters.
Conclusion :

14. • John S Rockey, Michael J waites, Neil L Morgan and Gary
Higton, 2001, “Industrial Microbiology – an introduction”,
Black well publishing . Page no- 163 –168.
• Samuel C, Prescott and Cecil G Denn, 2011, “Industrial
Microbiology”, Agrobios(India). Page no- 721 -725.
• Tanuja Singh and S S Purohit, 2011, “Fermentation
Technology”, Agrobios(India). Page no – 195 – 205.
References :