Accidental Discovery:

Penicillin
Presented by: Shruti Awari
Roll No: 14PHA1030

Story of Discovery
Fleming noticed a Petri dish containing
Staphylococcus that had been mistakenly left
open, was contaminated by blue-green mould
from an open window, which formed a visible
growth. There was a halo of inhibited bacterial
growth around the mould. Fleming concluded
that the mould released a substance that
repressed the growth and caused lysing of the
bacteria

When I woke up just after

dawn on September 28, 1928,
I certainly didnt plan to
revolutionize all medicine by
discovering the worlds first
antibiotic, or bacteria killer.
But I guess that was exactly
what I did.

 The development of penicillin for use as a

medicine is attributed to the Australian Nobel
lareate Howard Walter Florey, together with the
German Nobel laureate Ernst Chain

STRUCTURE

 Chemical structure was determined by Dorathy

Hodgkin using X-ray crystallography
Common core skeleton of the penicillins:
PENAM
Molecular Formula:R-C9H11N2O4S
Key structural feature: four membered -lactam
ring which is fused to a five-membered
thiazolidine ring.
WHY?

 The fusion of these two rings causes the -lactam

ring to be more reactive than monocyclic lactams.
This is because the two fused rings distort the lactam amide bond and therefore removes the
resonance stabilisation normally found in these
chemical bonds.

Mode of Action
All penicillin derivatives produce their
bacteriocidal effects by inhibition of bacterial
cell wall synthesis.

 The molecular targets for the antibacterial activity

of the penicillin and related -lactam antibiotics
are a group of bacterial enzymes known as
penicillin binding proteins(PBPs or
transpeptidase)
The PBPs are essential for the final stages of
bacterial cell wall synthesis.
Penicillin inhibits PBPs thereby inhibiting
bacterial cell wall biosynthesis, which eventually
results in bacterial cell lysis.

Administration
Penicillin G- Intravenous use
Penicillin V- oral use
Procaine Penicillin and Benzathine PenicillinI.M.

Penicillin G
Effective only against gram-positive bacteria.
Broken down in the stomach by gastric acids and
is poorly and irregularly absorbed into the blood
stream
Many disease producing staphylococci are able
to produce an enzyme capable of inactivating
penicillin-G.
Various semisynthetic derivatives have been
produced which overcome these shortcomings.

Production
Penicillin is a secondary metabolite of certain
species of Penicillium and is produced when
growth of the fungus is inhibited by stress
Penicillium cells are grown using fed batch
culture, in which the cells are constantly
subjected to stress

 A medium of corn steep liquor (a by product of starch

manufacture), yeast extract and others substrates added
to the fermentor
After 40 hours, Penicillin begins to be secreted by the
fungus
The mould mycelium (cell matter) is filtered from the
harvested product.
Penicillin is extracted in the organic solvent:
butylacetate, in which it dissolves.
Potassium salts are added and a penicillin preciptate is
formed, this is washed and dried.

John Clarke Seehan

Synthetic Penicillin
In 1946 chemist John Clarke Seehan at MIT
dedicated himself to tackling the penicillin problem
After 9 years he was successful in creating a general
total synthesis of penicillin
How?
It was made possible with the isolation of Penicillin
6-APA, the nucleus of the penicillin molecule,
which, once isolated allowed for the creation of
various and specific types of penicillin by stringing
molecules from this stable nucleus

There are three main instances where penicillins

can be used, these are:
To help fight off a bacterial infection e.g.
tonsillitis
To prevent infection for someone with a
weakened immune system due to existing
illness/condition e.g. someone with sickle cell
disease
To give someones immune system help if they
are undergoing treatment which could leave
them vulnerable to infection

Acknowledgements

Chemwiki
Wikipedia
Chemistry explained
YouTube

Thank You