Rewrite A13 (group A3,A10 and A13)
Due 02/23/2013
Overview of Penicillin
The onset of advancements in drug discovery in the 20th century influenced the discovery
and production of key antibiotics. Penicillin was one of the many significant antibiotics
chemicals, which can kill or stop the growth of disease, to be discovered by Alexander Fleming
during this period. The advent of penicillin reduced “deaths by infectious diseases to only onetwentieth” of what they were estimated as in 1900s (Fogel). Penicillin was soon known as a
universal drug or “wonder drug” from its biological and organic properties that resulted in
apoptosis of bacterial cells and the derivatives created that would further increase its potency.
The introduction is good but simple. It might be helpful to add some sentences about how it is
useful today and further discovery of modern medicine.
Penicillin was established as the “wonder drug” in the pharmaceutical industry by its
efficacy and potency in treating bacterial infections and reproduction. Penicillin was discovered
by Alexander Fleming in 1929 from the isolation of a mold, Penicillium notatum. Neighboring
cell plates of the mold’s secretion showed diminishing cell growth, indicating to Fleming of
Penicillin’s unique ability. Fungal colonies streaked onto plates containing bacterium
Staphylococcus aureus, exhibited transparent colonies due to the lysing of the bacterium’s cell
walls (Discovery and Development of Penicillin). The effects of Penicillin were evident in its
ability to prevent bacterial cell growth in their reproductive phase, mitosis. The potency of
Penicillin instantaneously sparked further research into the fungal metabolite in its ability to
control bacteria. Although Fleming was the initial scientist to discover Penicillin, he was unable
to purify for commercial use due to its instability. Commercial production of the Penicillin would
not be possible until the work of Howard Florey, Ernst Chain, and Norman Heatley at Oxford
University during 1938. Florey and Chain focused upon improving purification methods and its
efficiency by incorporating various types of mold. Of these were P. chyrsogenumby discovered
by Mary Hunt which revolutionized Penicillin production in the drug industry. In comparison to
Penicillium notatum, P. chyrsogenumby doubled penicillin growth in the drug industry
(Development and Discovery of Penicillin). Florey and Chain further enhanced Penicillin
production through the use of corn steep liquor significantly increased the yield of Penicillin.
Their research in Penicillin’s “growth, extraction, and purification” allowed for distribution on an
industrial scale or widespread use (Fogel). Penicillin quickly became a valuable drug in the
pharmaceutical industry in its high activity rate in bacterial control and low toxicity to the human
body. The paragraph is too long perhaps split it into two paragraphs. One paragraph could be all
about how it was discovered and how Alexander Fleming came up with the idea. Second
paragraph could be about how it was produce as a drug and the effect of cell growth. Remember
to also include references.
The unique biological properties of Penicillin allow for its inhibition of bacteria growth.
Inhibition of cell growth is caused by its ability to prevent the formation of new cell walls.
Specifically, the cross-linkage of small peptide chains in peptidoglycan is prevented, causing the
lack of cell wall polymer in bacteria. The beta-lactam ring of Penicillin irreversibly binds to an
enzyme active site on the bacterial cell. From this, the attempt at developing a new cell wall
during mitosis is prohibited (Shodor). The lack of a cell wall and for the resulting daughter cells
“makes them more susceptible to osmatic lysis.” Furthermore, the bacterial cells are forced to
grow at a larger size, reducing the frequency of cell division (Penicillin and Other Antibiotics).
Although Penicillin is effective in preventing further bacterial cell growth, it is limited to
affecting only newly produced cells and not pre-existing bacterial cells. Clearly, the biological
properties of Penicillin allow for it to become a universal drug in bacterial treatment. It would be
nice to add some pictures of cell divisions.
In addition to Penicillin’s distinctive biological properties were its organic properties. Its
organic structure was deduced to be of a beta-lactam derived from valine and cysteine with a
tripeptide intermediate replaced with an acyl group (Shodor). The organic structure exhibited a
close relation to variations of Penicillin through the natural occurrence of Penicillin G and
Penicillin V. Their differing chemical structures allow for varying properties in which Penicillin
V is much more effective in acidic environments in comparison to Penicillin G. Both however,
are only effective in the prevention of bacterial growth in Gram-positive bacteria, those with a
cell wall that consist of thick layers of peptidoglycan. Ideally, Penicillin G and Penicillin V were
used for treating pathogens that invaded the human body via wounds (Penicillin and Other
Antibiotics). The restrictions of Penicillin G and Penicillin V called for the synthesis of new
variations that could be effectively applied to certain environments thus leading to the
development of semi-synthetic penicillin. The natural versions were modified by “removing the
acyl from 6-aminopenicillanic acid,” allowing for the addition of various acyl groups with
specific properties. From this, varying types of Penicillin were deduced such as Ampicillin,
Carbenicillin, and Oxacillin. Each had their unique properties where they were “resistant to
stomach acid, resistant to penicillinase, and possess extended range of activity against Gramnegative bacteria,” respectively. Evidently, the chemical structure of Penicillin allowed for it to
rapidly become the universal drug in its versatility in the drug industry. Adding some pictures
such as the relation of Penicillin G and V. or even the difference between gram positive and
negative.
Within recent years bacterial resistance to penicillin has become more common.
Penicillin usually falls into two categories, Biosynthetic and semi-synthetic. Biosynthetic is
natural penicillin that is harvested from mold through fermentation, while semi-synthetic
chemically modified derivatives allow the drug to have new properties. Penicillinase is the
enzyme within bacteria that has been developed to destroy penicillin. Bacteria that contain
penicillinase have a resistance to penicillin. The most common name for this group of enzymes
that are produced by bacteria is Beta-lactamase. Beta-lactamases provide resistance against antibiotic due to their ability to break down the structure of the anti-biotic. This enzyme uses the
mechanism of hydrolysis; the enzyme breaks the beta-lactam ring open. By breaking open the
beta lactam ring, this deactivates the molecular antibacterial property. Due to this reason it is
very important that penicillin is used with utmost care, due to the fact that there may be bacterial
resistance to this drug. Due to this family of enzymes, beta-lactamases, new derivatives of
penicillin were developed, such as cephamycins and carbapenems. The last couple of sentences
uses “due to this” maybe changing the words a bit. This paragraph could also use a picture of
how the beta lactam ring breaks open due to hydrolysis.
Within this group of beta-lactam antibiotics, carbapenems have the highest resistance to
most beta-lactamases. This is due to the carbapenem structure. From its structure, carbapenems
have similar 5 carbon rings feature as it parent compound, penicillin, with an additional
unsaturated bond between C2 and C3 and a substitution of carbon at C1 for sulfur. The
replacement of carbon 1 with sulfur helps contribute in the potency and spectrum of the
compound against β- lactamases bacteria with higher stability. Furthermore, its stereochemistry
of a trans configuration at C5 and a R chirality center at C8 increase its antimicrobial spectrum,
which corresponds to higher resistance to hydrolysis by the β- lactamases. In term of origin,
Carbapenem was developed from carbapenem thienamycin. Carbapenem thienamycin was first
discovered in 1976 through streptomyces. Stretomyces are a family of bacteria belonging to the
streptomycetaceae family. Thienamycin is the most potent naturally produced anti-biotic. This is
an excellent drug against both gram positive and negative bacteria and is resistant to Betalactamases enzymes. Unlike penicillin, thienamycin is a naturally occurring antibiotic that has
resistance to beta-lactamases. One important substituent of the two structures, carbapenem and
thienamycin, that cause relatively high resistance to hydrolysis of most β- lactamases is the
hydroxyethyl side chain of thienamycin. The side chain has an acyl amino substituent on the βlactam ring, which provides potent antibacterial and inhibitory activity. Although these two βlactamases inhibitors provide greatest potency against the bacteria, more resistance bacteria, such
as multidrug-resistant pathogens, are emergences. Due to the vast library of bacteria that has
been discovered to have anti-biotic resistance, more and more drugs have to be discovered that
are capable of destroying bacteria. This paragraph can be split into two. One paragraph could be
all about carbapenems. Second paragraph could be about thienamycin. Remember to also include
references and pictures.
Carpaenems, having the broadest spectrum of activity and against gram-positive and
negative bacteria, are used to treat complicated bacterial infections in clinical uses. This
penicillin β group is combined with an antibiotic, which targets gram- positive if use to treat
severe hospital-acquired infection as empirical treatment. The antibiotics contain groups of
compounds that vary in the types of treatment for patients, which include “antipseudomonal,
anti-methicillin-resistant S. aureus (MRSA) carbapenems (i.e., cationic and dithiocarbamate
carbapenems), orally available carbapenems, trinem carbapenems, and a dual quinolonylcarbapenem (Antimicrob. Agents Chemother. November 2011 vol. 55 no. 11 4943-4960)”.
Interesting, the first oral carpaenems invented is Tebipenem-pivoxil, which increase the intestinal
absorption for patients, particularly children with pneumonia illness. Although Carpaenems are
beneficial, careful care prescribed from doctors should be considered to heal the necessary
infections. You have mentioned carbapenems from the pervious paragraph why not add this to
that paragraph. This paragraph is not needed.
With today’s modern technology and need for medication, Anti-biotic are not developed
on a micro but macro scale. Industrial production of penicillin and also other beta-lactam
antibiotics are very tedious task that require constant monitoring. Most of these antibiotics
require fermentation, and fermenters are used for fermentation. The concepts to consider within
industrial fermenters are functionality and economics. Within the economic aspect the fermenter
has to be easy to “operate, flexible, low power consumption, stable, cheap”. The functional
aspects of the fermenter have these following characteristics: a “high gas/liquid mass transfer,
reasonable heat transfer aggregation prevention, bulk flow, and nutrient transfer”. Mass transfer
is a very important aspect of the fermenter because it facilitates the flow of oxygen within the
tank. Oxygen is very important because mold is an aerobic organism; therefore, it is important to
have a good flow of oxygen between molds and liquid. Heat transfer is a very important because
metabolism is an exothermic process. Therefore there has to be systems that cool the reactor.
There has to be a continuous culture that allows liquid to be added in and simultaneously
released. Along with this there are special conditions for penicillin; most penicillin’s require a pH
of 6.5 for growth this is mostly maintained by the addition of sodium hydroxide (NaOH). These
are the optimum conditions for facilitating the production of penicillin. This is a good paragraph
about how medicine are made today. Maybe adding a specific company who does this.
The rapid growth of Penicillin in the early 20th century has been exhibited in its ability to
treat bacterial infections and its versatility. Its discovery and growth as a drug enabled for the
advancement in medicine and drug discovery in which previous ailments have an easily
identifiable cure. Its efficacy influenced the development of new antibiotics while remaining as a
front-line antibiotic. Ultimately, Penicillin can be regarded as the universal or wonder drug to a
significant extent due to its versatility and potency in the medicinal environment. The conclusion
is good by explaining what this essay is about. Overall, this essay is good for an overview of
penicillin. It could be better by adding pictures and reviewing some of the paragraphs. There are
paragraphs that can be split into two. There is one paragraph that is not needed. Also, don't forget
about references and grammar check Good job!