Ida Kusuma Samuel P.

Sianturi Monica Julius Lie PE-5

 One of the earliest discovered and widely used antibiotic

agents. Derived from the Penicillium fungi. The beta-lactam group of antibiotics Medicine that fight bacteria infection

 First found in 1928 by Sir Alexander Fleming.

Fleming was developing staphylococci. But it is

contaminated by blue-green mould. The mould was dissolving the bacteria

 He found that it was from the

Penicillium family.

Fleming presented his findings in 1929, but they raised

little interest. Then, Howard Florey and Ernst Chain were able to develop a powdered form of penicillin. In 1941 the first human was successfully treated

A. Fleming

E. Chain

H. Florey

 Done by -Lactam binding to the enzyme

transpeptidase
Enzyme transpeptidase resembles a protein needed

for production of cell wall.

 Penicillin binds to cell wall of bacteria, prevents peptide

chains from linking, and lyses it.

 Primary metabolites are

produced during active cell growth, and secondary metabolites are produced near the onset of stationary phase. Like all antibiotics, penicillin is a secondary metabolite, so is only produced in the stationary phase.

The industrial production of penicillin was broadly classified in to two processes namely: Upstream processing
Upstream processing encompasses any technology that leads to the synthesis of a product. Upstream includes the exploration, development and production.

Downstream processing
The extraction and purification of a biotechnological product from fermentation is referred to as downstream processing.

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

 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. Corn steep liquor (CSL) Ammonium sulphate and ammonium acetate can be used as nitrogenous sources.

NITROGEN SOURCES:

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

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

The extraction and purification of a biotechnological product from fermentation which commonly involves filtration to separate the microbial cells from the liquid medium, followed by chemical purification and concentration of the product.

BIOMASS REMOVAL

ADDING OF SOLVENT

STORAGE

STAGES

EXTRACTION

FLUID BED DRYING

CENTRIFUGAL EXTRACTION

- Filtration, commonly using Rotary Vacuum Filter

- Addition of Phosporic Acid

Dissolving Penicillin using Butyl Acetate or Amyl Acetate

Separate the solid waste from the liquid component which contains the penicillin

Disk centrifuge- One of the most common type of centrifuge for large scale production

- Obtaining certain purity level by mixing the

dissolved penicillin with phosphate buffer, chloroform solution and ether solution - Penicillin precipitation using Sodium bicarbonate
Basket Centrifuge- Commonly used in the removal of solids in this case Penicillin salt

Removing any remaining moisture present in the powdered penicillin salt.

Powdered penicillin being blowned by hot air

Fluid bed drying tube

Stored in containers and kept in a dried environment

The White Penicillin-Sodium salt

 For parental use, the antibiotic is packed in sterile vials

as a powder or suspension. For oral use, it is tabletted with further addition of film coating.