PENICILLIN

ANTIBIOTICS
 Products of secondary
metabolism of microorganisms
which inhibit growth
processes of other organisms
 ALEXANDER FLEMING
was the 1st scientist to discover
the antibiotic effect of
microorganisms.
•Penicillins act against gram positive bacteria.
•Penicillins differ on the basis of different side groups “R”.
•Βeta- Lactam ring responsible for antibiotic activity.
•Most of the penicillins are 6-APA (6-Aminopenicillinic acid) derivatives.
•When there is no addition of side chain precursors, NATURAL
PENICILLINS are produced.
•When side chain precursors are added, BIOSYNTHETIC PENICILLINS
are produced.
•SEMI-SYNTHETIC PENICILLINS are produced by chemically/
enzymatically splitting Penicillin G to form 6-APA.
NATURAL PENICILLINS :
Benzylpenicillin (Penicillin G)

BIOSYNTHETIC PENICILLINS
: Phenoxymethylpenicillin
(Penicillin V)

SEMI-SYNTHETIC PENICILLINS : Oxacillin, Ampicillin

INDUSTRIAL PRODUCTION OF PENICILLIN
LYOPHILIZED CULTURE (SPORES)

INOCULUM CULTIVATION

PREFERMENTATION

PRODUCTION FERMENTATION

COOLING TANK

PURIFICATION
PARAMETERS FOR
PENICILLIN
FERMENTATION
 Submerged type fermentation
 Aeration rate : 0.5-1.0 vvm
 Temperature: 25-27°C
 Precursor: Phenyl acetic acid (for Penicillin G) added
continuously
 Growth phase : 40 hours
 Production phase: 120-180 hours
 pH : 6.5
 Critical parameters: oxygen supply and sugar
concentration
 Production media contains lactose (1%), CaCO3 ,
Cornsteep Liquor (8.5%), glucose (1%), NaH2PO4
(0.4%), Phenyl acetic acid (0.5 gm).

 The 3 phases of production include:

(1) PHASE 1:
 Growth of mycelium
 Low yield of antibiotic
 Lactic acid present in CSL is utilized at a maximum
rate by microorganism
 Lactose used slowly
 Ammonia is liberated into medium, thus increasing
pH
(2) PHASE 2 :
Intense synthesis of penicillin
Mycelium mass is sharply
reduced due to rapid utilization
of glucose and ammonia
pH remains unchanged

(3) PHASE 3:
Concentration of antibiotic
decreases in medium
Autolysis of mycelium starts
Ammonia is liberated, thus
increasing the pH slightly.
RECOVERY OF PENICILLIN