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E. Chain H. FloreyA. Fleming
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Primary metabolites areproduced during active
cell growth, and
secondary metabolites
are produced near the
onset of stationary phase.
Like all antibiotics,
penicillin is a secondarymetabolite, so is only
produced in the stationary
phase.
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The industrial production of penicillin wasbroadly classified in to two processes namely:
Upstream processingUpstream processing encompasses any technology thatleads to the synthesis of a product. Upstream includesthe exploration, development and production.
Downstream processingThe extraction and purification of a biotechnologicalproduct from fermentation is referred to as downstreamprocessing.
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Upstream Processing
Inoculum Preparation
The medium is designed to provide the organism with allthe nutrients that it requires.
Inoculation method: Submerged technique
Spores: Major source of inoculum
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CARBON SOURCES:Lactose acts as a very satisfactory carbon compound, provided that isused in a concentration of 6%. Others such as glucose & sucrose maybe used.
NITROGEN SOURCES:
Corn steep liquor (CSL)Ammonium sulphate and ammoniumacetate can be used as nitrogenous sources.
MINERAL SOURCES:Elements namely potassium, phosphorus, magnesium, sulphur, zinc
and copper are essential for penicillin production. Some of these areapplied by corn steep liquor.
Calcium can be added in the form of chalk to counter the naturalacidity of CSL
PAA: precursor
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The medium is inoculated witha suspension of conidia ofPenicillium chrysogenum.
The medium is constantly
aerated and agitated, and themould grows throughout aspellets.
After about seven days, growth
is complete, the pH rises to 8.0or above, and penicillinproduction ceases
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The extraction and purification of a biotechnologicalproduct from fermentation which commonly involvesfiltration to separate the microbial cells from the
liquid medium, followed bychemical purificationand concentration of the product.
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BIOMASS REMOVAL
ADDING OFSOLVENT
CENTRIFUGAL
EXTRACTION
EXTRACTIONSTORAGE
FLUID BED DRYING
STAGES
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- Filtration, commonly using Rotary Vacuum Filter
- Addition of Phosporic Acid
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Dissolving Penicillin using Butyl Acetate or AmylAcetate
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Disk centrifuge- One of the most common
type of centrifuge for large scale production
Separate the solid waste from the liquidcomponent which contains the penicillin
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- Obtaining certain purity level by mixing thedissolved penicillin with phosphate buffer,chloroform solution and ether solution
- Penicillin precipitation using Sodium bicarbonate
Basket Centrifuge- Commonlyused in the removal of solids inthis case Penicillin salt
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Removing any remaining moisture present in the
powdered penicillin salt.
Fluid bed drying tube
Powdered penicillin being blownedby hot air
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Stored in containers and kept in a dried environment
The White Penicillin-Sodium salt
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For parental use, the antibiotic is packed in sterile vialsas a powder or suspension.
For oral use, it is tabletted with further addition of filmcoating.
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