Manufacture of Penicillin by Fermentation

Introduction:
 The first discovered natural antibiotic was Penicillin.

 Penicillin was obtained from multicellular fungi, “Penicillium molds”.
 In 1928, Sir Alexander Fleming made one of the most important contributions to the field of antibiotics.
 Penicillin are two types.These are P. notatum & P. chrysogenum (also called Penicillin G)
 Even from these two P. chrysogenum is high yielding strain and therefore most widely used as production strain.
Structure of Penicillin:
 The basic structure of penicillin consists of a thiozolidine ring condensed with a B-lactum ring.
 Natural penicillin is 6-amino-penicillinic acid (6APA).
 Penicillin is a group of compounds having common basic nucleus, 6-amino penicillinic acid (6-APA).
 6-APA contains ring like structure termed as a β-lactam ring.
Manufacture of penicillin by fermentation Process
These are the following parameters and conditions should maintain during the production of penicillin
 Method: fed-batch or batch
 Raw material/Substrate: glucose, phenoxyacetic acid (fed component used for production of side chain), Corn steep liquor, Additional
nitrogen source ie, soyameal, yeast extract, Lactic acid, inorganic ions, growth factors
 Fermenter: stirred tank or air lift tank
 pH: set at 5.5 to 6.0 which increased upto 7-7.5 (optimum) due to liberation of NH3 gas and consumption of lactic acid. If pH is 8 or more,
CaCO3 or MgCO3 or phosphate buffer is added
 temperature: 25-27 °C
 aeration: 0.5-1 vvm (initially more, latter less O2 ), vvm means VVM (volume of gas per volume of liquid per minute).
 agitation: 120-150 rpm)
 time: 3-5 days
 antifoam: edible oil (0.25%)
 Carbon Source: Lactose, glucose & sucrose
 Nitrogen Source Ammonium salts such as ammonium sulfate, ammonium acetate, ammonium lactate or ammonia gas are used for this
reason.
 Mineral Source: These elements include phosphorus, sulfur, magnesium, zinc, iron, and copper which generally added in the form
of water soluble salts.
Process description for production of penicillin by fermentation process
In the manufacture of penicillin, fermentation is the preferred route. Penicillin production consists of three stages. These are fermentation
extraction and purification of penicillin. In fermentation process the fermentation substrate consists mainly of the sucrose found in corn steep
liquor and lactose together with minerals and mycelia are fed to the fermentation tank.
The whole process is aerobic (it requires air). The fermentation is carried out over 4 or 5 days at 25-27°C. This gives a yield of about 0.5%
penicillin. The mycelium, the mold cells plus insoluble metabolites, is filtered off in a coated rotary drum filter. The filtrate is adjusted the pH 2
with sulphuric acid. At this pH, the penicillin exists as an undissociated acid and it is extracted in extraction process by adding organic solvents
like butyl acetate or ketone; consequently, it is soluble in organic solvents. After extraction the solution is decolourised and impurities are
removed by activated carbon. The penicillin is then precipitated by addition of inorganic solvent like solution of potassium acetate or Na salt or
KOH. The precipitated penicillin converts in to crystalized salts of penicillin. Then it is filtered and dried and formed the solids of penicillin.
Application of penicillin:
 Clinical uses of penicillin:
 naturally effective antibiotics against gram + bacteria
 used for treatment of bacterial endocarditis
Fermentation mold for production of penicillin G

Butyl acetate
organic solvent
NOT REQUIRED. JUST FOR UNDERSTANDING
Keywords:
Mycelia: It is a root-like structure of a fungus consisting of a mass of branching, thread-like hyphae.
Spore: Spores are the main reproductive units for fungi and are usually single cells.
A spore is a cell that certain fungi, plants (moss, ferns), and bacteria produce.
Incolution: Injection or Microbiologists collect a small sample of microbes from a given source (we call this small sample an "inoculum") and
place them into a medium that contains the nutrients needed for growth.
Precursur: a substance, cell, or cellular component from which another substance, cell, or cellular component is formed
Strain: In biology, a strain is a genetic variant, a subtype or a culture within a biological species.
Fermentation broth: fermentation liquid or soup
Anti-foam agents works (used lard oil, octadecanol and silicones ): Maximum accumulation of penicillin. Ease of extraction and purification
of antibiotics.
Mold: is one of the structures certain fungi can form.
What are the top pharma industries in India?

Top Pharma Companies in India as on Dec-2022
Sun Pharmaceutical Industries Ltd.,
Cipla Ltd.
Divis Laboratories Ltd.
Dr. Reddys Laboratories Ltd.
Apollo Hospitals Enterprise Ltd.
Torrent Pharmaceuticals Ltd.
Abbott India Ltd.
Max Healthcare Institute Ltd.
References
https://youtu.be/RG6BeXpB2jc https://youtu.be/pJSXaiWahvE

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Introduction:

 The first discovered natural antibiotic was Penicillin.

Fermentation mold for production of penicillin G

Mycelia: It is a root-like structure of a fungus consisting of a mass of branching, thread-like hyphae.

Fermentation broth: fermentation liquid or soup

Mold: is one of the structures certain fungi can form.

What are the top pharma industries in India?

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