2. Penicillin: group of antibiotics ,treat wide
range of bacterial infections
Discovered by A.flemming in 1928
,produced by a fungi called penicillium
notatum in a stance of accidental
discovery
World war 2 leads to its urgency to
be produced in large scale
Penicillium chrysogenum proved to be
highly efficient in growth ,thus using in
industries till today.
3. Selection of strain
at the end of the Second World War using
the fungus Penicillium notatum, the process
yielded one milligram per cubic decimeter.
Today, with a use of a different
species (Penicillium chrysogenum) and
improved extraction procedures the yield is
50 grams per cubic decimeter.
so by improving strain,product can be
enhanced
5. • Medium
P.chrysogenum usually contain its carbon source in corn
steep liqour and glucose, also contains salts MgSO₄, K₃PO₄
and sodium nitrates
• Heat sterilization
Pressurized heat is used and medium is heated to 121°C at
30 psi
High temp and short time duration is used to prevent
degradation of certain medium component
• Specific conditions for penicillin
Fungus form filamentous broths→high viscosity→hindrance
to O₂ → bubble column used to mix O₂ equally and to
agitate medium
7. Production of penicillin
• Penicillin→secondary metabollite →produces in stress
conditions
• For primary metabolism media should be focused to attain
maximum growth and biomass production
• After the achievement of desired biomass →strave the
culture → limiting C and N →triggers antibiotic production
• Fed batch method is used →allows to add substrate in
small increments →to even change the substrate if we
desire
8. Seed culture
• First penicillin chrysogenum spores are added with liquid
medium when it has grown to acceptable amount, it is
inocuated into fermentors
9. fermentation
• It is done at fed batch fermentors →substrate is added in
large amount at the very beginning as it retards penicillin
production
• Temp is 20-25 for mold ,pressyer is higher then 1 atm to
prevent contamination from external environment
• pH is kept 6.5
• After about 40hours penicillin begins to secreted
• After 7 days growth completed,pH increases to 8 which
ceases penicillin synthesis
10. Removal of biomass
• Filteration is carried out as bioseparation to rempve
biomass from culture
• Rotatory vaccum filters are used
• After filteration phosphoric acid is introduced that lowres
ph to 6,5 to prevent loss of activity of penicillin
•Addition of solvent
• Organic solvents ae added to disslove penicillin present in
filterate
• At this point penicillin is present in liq..and any other solid
is considered as waste
11. Centrifugal extraction
• To remove solid waste
• Extraction
• Requires series of steps to obtain better purity of penicillin
• Acetate solution is mixed with phosphate buffer, followed
by chloroform, mixed again with phosphate buffer and
then ether
• Penicillin is present in high conc. In ether and it will be
mixed with solution of sodium bicarbonate to obtain
penicillin sodium salt
• It allows penicillin to be stored at room temp
• Basket centrifugation is done to remove salt from liquid
12. Fluid bed drying and storage
• Necessary to remove any moisture in salt
• Stored in containers and kept in dried environment
• The penicillin is modified chemically to make semi
synthetic penicillins
