1. The document discusses the production of penicillin from Penicillium chrysogenum fungus. It describes the fermentation process using lactose and yeast extract as carbon and nitrogen sources. 2. Downstream processing such as filtration and solvent extraction is used to purify the penicillin from the fermentation broth. Purification involves dissolving the penicillin and precipitating it as a potassium salt. 3. Semi-synthetic derivatives of penicillin like ampicillin and amoxicillin are also produced. The fermentation takes place in batch cultures over 160-200 hours for maximum yield of the secondary metabolite penicillin.

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KWEZI MWAKA JULIUS 12/U/494
MICROBIOLOGY INDIVIDUAL REPORT ON MANUFACTURE OF PENICILLIN
Objectives
 To be able to identify useful products from microorganisms.
 To be able to identify the microorganisms used and the main stages in the production of
penicillin.
 To be able to describe how downstream processing is carried out to extract and purify the
end‐product of fermentation.
Abstract
During production the source of carbon is lactose, that of nitrogen is yeast and that of energy is
glucose. It uses anaerobic fermentation in a small fermenter of 40 to 200dm3since a large has
difficulty in aeration at an optimum temperature of 25-27℃. The product normally spends 40
hours in the fermenter after main increase in fungal mass. During production of penicillin we use
corn steep liquor as a substrate in a batch culture since it is a secondary metabolite. There are
three processes involved in downstream processing which include filtration of liquid, extraction
from filtrate by countercurrent of butyl acetate.
The fungus used is Penicillin chrysogenum
The structure

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General uses of penicillin
Penicillin are useful against infections in many parts of the body, including the mouth and throat,
skin and soft tissue, tonsils, heart, lungs, and ears. However, since many bacteria are resistant to
penicillin, it is often wise to do a culture and sensitivity test before using penicillin. In some
cases, there are only a few types of bacteria that are likely to be a problem, and so it is
appropriate to use penicillin without testing. For example, dentists often prescribe penicillin to
prevent infections after dental surgery
Introduction
This antibiotic is manufactured commercially using Penicillium chrysogenum. The penicillin is
produced in large stainless steel fermenters, which have a capacity of around 10000 dm3.
The fermenter is sterilised by steam and then loaded with a sterilised growth medium for the
Penicillium chrysogenum to feed on, containing lactose, amino acids and mineral salts amongst
other things. The temperature and pH are monitored constantly to ensure that the conditions in
the fermenter are optimum for the bacteria. The fermenter is also continuously stirred and sterile
air fed in. The penicillin in the resultant broth after 160 – 200 hours of fermenting is obtained by
solvent extraction.

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The process flow
The process
Penicillin is produced by the fungus Penicillium chrysogenum which requires lactose, other
sugars, and a source of nitrogen (in this case a yeast extract) in the medium to grow well. Like all
antibiotics, penicillin is a secondary metabolite, so is only produced in the stationary phase. It
requires a batch fermenter, and a fed batch process is normally used to prolong the stationary
period and so increase production. Products in a fermenter are impure and dilute, so need to be
purified by downstream processing which usually involves filtration to separate the microbial
cells from the liquid medium, followed by chemical purification and concentration of the
product.

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NB: Downstream processing can account for 50% of the cost of a process. Downstream
processing is relatively easy since penicillin is secreted into the medium (to kill other cells), so
there is no need to break open the fungal cells. However, the product needs to be very pure, since
it being used as a therapeutic medical drug, so it is dissolved and then precipitated as a potassium
salt to separate it from other substances in the medium.
The resulting penicillin (called penicillin G) can be chemically and enzymatically modified to
make a variety of penicillins with slightly different properties.
These semi‐synthetic penicillins include penicillin V, penicillin O, ampicillin and amoxycillin.
The pathway of penicillin synthesis

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Appendix
A graph showing production of penicillin with available nutrients.
References
1. Garrod, L. P. (1960). "Relative Antibacterial Activity of Three Penicillins". British
Medical Journal 1 (5172): 527–29. doi:10.1136/bmj.1.5172.527
2. http://www.encyclopedia.com/topic/penicillin.aspx at 9:26 on 27th /03/2015
3. Kiel JAKW, van den Berg MA, Fusetti F, Poolman B, Bovenberg RAL, Veenhuis M, van
der Klei IJ: Matching the proteome to the genome: the microbody of penicillin-producing
Penicillium chrysogenum cells.
4. Funct Integr Genom 2009, 9:167-184. PubMed Abstract | Publisher Full Text
5. http://www.botany.hawaii.edu/faculty/wong/BOT135/Lect21b.htm