Roles of Microbes in Pharmacy.

Introduction
Micro-organisms (or microbes for short) play a very important role in
our lives. Some microbes cause disease which are usually refer to be
pathogenic but the majority are completely harmless. Most microbes are
very small living organisms that human unable to see them with naked
eyes but they may still observe these tiny creatures under microscope
that are able to magnifies them up to 1000 times their original size. These
microscopic organisms play a key role in sustaining life on earth, fixing
gases and breaking down dead plant and animal matter into simpler
substances

that

are

used

at

the

beginning

of

the

food

chain.

Biotechnologists can also exploit the activities of microbes to benefit

humans, such as in the production of medicines, enzymes and food. They
are also used to breakdown sewage and other toxic wastes into safe
matter. This process is called bioremediation.
The principal pharmaceutical interest was traditionally focusing
upon microorganisms to control, metabolism exploitation for manufacture
of the medicines which is a growing knowledge area that have
increasingly important not merely in pharmacy field but also other
disciplines employed in pharmaceutical industry.

Antibiotics
What is antibiotics?
The term antibiotic is used in several different ways: originally an
antibiotic was defined as a naturally occurring substance that was
produced by one microorganism that inhibited the growth of, or killed,
other microorganisms, i.e. an antibiotic was a natural product, a microbial
metabolite. More recently the term has come to encompass certain
synthetic agents that are usually used systemically (throughout the body)
to treat infection. (Hugo and Russell, 1998) In pharmacy field, antibiotics
work by interfering with the formation of the bacteriums cell wall or its
cell contents. Antibiotics take advantage of the difference between the
structure of the bacterial cell and the hosts cell. They either prevent the
bacterial cells from multiplying so that the bacterial population remains
the

same,

allowing

the

hosts

defence

mechanism

to

fight

the

infection or kill the bacteria, for example stopping the mechanism

responsible for building their cell walls.
Perhaps one of the most important discoveries regarding the beneficial
use of fungi for humans was the identification in 1929 by Sir Alexander
Fleming that an isolate of Penicillium notatum produced a substance
capable of killing Gram-positive bacteria. An antibiotic can also be
classified according to the range of pathogens against which it is effective.
For example, Penicillin G will destroy only a few species of bacteria and is
known as a narrow spectrum antibiotic. Tetracycline is effective against a
wide range of organisms and is known as a broad spectrum antibiotic.

Vaccination
A vaccine is a substance that is introduced into the body to
stimulate the bodys immune response. In healthcare services, it is given
to patients in order to prevent an infectious diseases cause by pathogenic
microorganism from developing that may cause the patient to become ill.
Vaccines itself are also made up from microbes but fortunately they
are commonly known to be given to patients via parenteral route or
injection. Fortunately, the microbes given are either dead or inactive so
that they are unable to cause the disease. But the antigen in the vaccine
is the same as the antigen on the surface of the disease-causing microbe.
The vaccine stimulates the body to produce antibodies against the
antigen in the vaccine. The antibodies created will be the same as those
produced if the person was exposed to the pathogen. If the vaccinated
person then comes into contact with the disease-causing microbe, the
immune system remembers the antibodies it made to the vaccine and can
make them faster. The person is then said to be immune to the pathogen.

Steroids
Steroids, such as cholesterol, are synthesized in almost all eukaryotic
cells, which use these triterpenoid lipids to control the fluidity and
flexibility of their cell membranes. Bacteria rarely synthesize such
tetracyclic compounds but frequently replace them with a different class
of triterpenoids, the pentacyclic hopanoids. The intriguing mechanisms
involved in triterpene biosynthesis have attracted much attention,

resulting in extensive studies of squalenehopene cyclase in bacteria and

(S)-2,3-oxidosqualene cyclases in eukarya. (Bode et al., 2003)
A steroid is a type of organic compound that contains a characteristic
arrangement of four cycloalkane rings that are joined to each other.
Examples of steroids used in pharmacy industries include the dietary fat
cholesterol, the sex hormones estradiol and testosterone, and the antiinflammatory drug dexamethasone. The core of steroids is composed of
twenty carbon atoms bonded together that take the form of four fused
rings: three cyclohexane rings (designated as rings A, B, and C in the
figure to the right) and one cyclopentane ring (the D ring). The steroids
vary by the functional groups attached to this four-ring core and by the
oxidation state of the rings. Sterols are special forms of steroids, with a
hydroxyl group at position-3 and a skeleton derived from cholestane.
Hundreds of distinct steroids are found in plants, animals, and fungi.
All steroids are made in cells either from the cycloartenol (plants) or
sterols lanosterol (animals and fungi). Both lanosterol and cycloartenol are
derived from the cyclization of the triterpene squalene.

Steroid Lanosterol
Steroid biosynthesis is an anabolic metabolic pathway that produces
steroids from simple precursors. A unique biosynthetic pathway is
followed in animals compared to many other organisms, making the
pathway a common target for antibiotics and other anti-infective drugs. In
humans and other animals, the biosynthesis of steroids follows the
mevalonate pathway that uses acetyl-CoA as building blocks to form

dimethylallyl pyrophosphate (DMAPP) and isopentenyl pyrophosphate

(IPP). In plants and bacteria, the non-mevalonate pathway uses pyruvate
and glyceraldehyde 3-phosphate as substrates.

Steroid Synthesis
The

non-mevalonate

pathway

or

2-C-methyl-D-erythritol

4-

phosphate/1-deoxy-D-xylulose 5-phosphate pathway (MEP/DOXP pathway)

of isoprenoid biosynthesis is an alternative metabolic pathway leading to
the formation of isopentenyl pyrophosphate (IPP) and dimethylallyl
pyrophosphate (DMAPP).
The classical mevalonate pathway or HMG-CoA reductase pathway is an
important cellular metabolic pathway present in all higher eukaryotes and
many bacteria. It is important for the production of IPP and DMAPP that
serve as the basis for the biosynthesis of molecules used in processes as
diverse as protein prenylation, cell membrane maintenance, hormones,
protein anchoring, and N-glycosylation.
In

contrast

biosynthesis,

to

the

classical

plants

malaria parasites have

mevalonate

and
the

ability

pathway

of

isoprenoid

apicomplexan protozoa such

to

produce

their

as

isoprenoids

(terpenoids) using an alternative pathway, the non-mevalonate pathway,

which takes place in their plastids. In addition, most bacteria including
important pathogens such

as Mycobacterium tuberculosis synthesize IPP

and DMAPP via the non-mevalonate pathway.

Enzymes
Enzymes are the large biomolecules that are required for the numerous chemical
interconversionsthatsustainlife.Theyaccelerateallthemetabolicprocessesinthe
bodyandcarryoutaspecifictask.Enzymesarehighlyefficient,whichcanincrease
reactionrates by 100 millionto 10 billiontimes faster than any normal chemical
reaction. Due to development in recombinant technology and protein engineering,
enzymeshaveevolvedasanimportantmoleculethathasbeenwidelyusedindifferent
industrial and therapeutical purposes. Microbial enzymes are currently acquiring
muchattentionwithrapiddevelopmentofenzymetechnology.Microbialenzymesare
preferredduetotheireconomicfeasibility,highyields,consistency,easeofproduct
modificationandoptimization,regularsupplyduetoabsenceofseasonalfluctuations,
rapid growth of microbes on inexpensive media, stability, and greater catalytic
activity.Microbialenzymesplayamajorroleinthediagnosis,treatment,biochemical
investigation,andmonitoringofvariousdreadeddiseases.Amylaseandlipasearetwo
veryimportantenzymesthathavebeenvastlystudiedandhavegreatimportancein
differentindustriesandtherapeuticindustry. (Gurung et al., 2013)

Enzymes applications
Ahigherthannormalconcentrationofamylasesmaypredictoneofseveral
medicalconditions,includingacuteinflammationofthepancreas,perforatedpeptic
ulcer,strangulationileus,torsionofanovariancyst,macroamylasemia,andmumps.
Inotherbodyfluidsalsoamylasecanbemeasured,includingurineandperitoneal
fluid. In various human body fluids the level amylase activity is of clinical
importance,forexample,indiabetes,pancreatitis,andcancerresearch.

LipasesisolatedfromGalleria mellonella(waxmoth)werefoundtohavea
bactericidal action on Mycobacterium tuberculosis (MBT) H37Rv. This
preliminary research may be considered as part of global unselected screening of
biologicalandothersamplesfordetectingnewpromisingsourcesofdrugs.Lipases
can be used as digestive aids. Lipases can be used in the treatment of malignant
tumorsastheyaretheactivatorsoftumornecrosisfactor.Humangastriclipase(HGL)
isthemoststableacidlipaseandconsideredtobeagoodtoolforenzymesubstitution
therapy. Earlier lipases have been used in the treatment of gastrointestinal
disturbances,dyspepsias,cutaneousmanifestationsofdigestiveallergies,andsoforth.
Lipase fromCandida rugosa synthesizes lovastatin, a drug that lowers serum
cholesterollevel.Theasymmetrichydrolysisof3phenylglycidicacidesterwhichisa
keyintermediateinthesynthesisofdiltiazemhydrochlorideisawidelyusedcoronary
vasodilatorandissynthesizedusingS. marcescens lipase.
Mutagenic and carcinogenic activity detection

In pharmacy, Carcinogens such as aflatoxin Bi, benzo(a)pyrene,

acetylaminofluorene, benzidine, and dimethylamino-trans-stilbene, are
shown to be activated by liver homogenates to form potent frameshift
mutagens. It is believed that these carcinogens have in common a ring
system sufficiently planar for a stacking interaction with DNA base pairs
and a part of the molecule capable of being metabolized to a reactive
group: these structural features are discussed in terms of the theory of
frameshift mutagenesis. It was proposed that these carcinogens, and
many others that are mutagens, cause cancer by somatic mutation. A

simple, inexpensive, and extremely sensitive test for detection of

carcinogens as mutagens is described. It consists of the use of a rat or
human liver homogenate for carcinogen activation (thus supplying
mammalian metabolism) and a set of Salmonella histidine mutants for
mutagen detection. The homogenate, bacteria, and a TPNH generating
system are all incubated together on a petri plate. With the most active
compounds, as little as a few Nano grams can be detected. In some other
cases, The Salmonela reversion test was used to measure the mutagenic
activites

of

urine

concentrates

from

individuals

chemotherapy agents for i.v. administration.

preparing

cancer