Pharmaceutical

BIOTECHNOLOGY

Lec 1
Maisra El-Bouseary
Lecturer of Microbiology

Email:
maysra_mohamed@pharm.tanta.edu.eg
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Introduction
Biotechnology:
Biotechnology is the application of
biological systems, organisms or
processes in manufacturing or service
industries.
It is a composite science, involving
microbiology, genetics, biochemistry
and engineering.
Biotechnology tree
History of Biotechnology:
 From tomb paintings of Ancient Egypt
we can tell that they had highly
developed bread making skills.
 Cheese, wine, yogurt and vinegar have
been made for centuries.
 The discovery of antibiotics in 1929, and
their large-scale production during
 the Second World War, created great
advances in fermentation technology.
Bread making. From the tomb of Kenamun, Sheikh Abd el-Qurna,
1550-1295 BC. Artist Ancient Egypt.
Important principles:
The cells' enzymes are used for:
a- Primary metabolism: generating energy and
biomass, and degrading substrates

b- Secondary metabolism occurs at specific

points in the life cycle rather than throughout the
life of the organism.
It is associated with changes in the organism, such as
spore formation or aging.
Examples of secondary metabolites are antibiotics,
terpenoids, polyketides and acetylene
(propene).
 Primary metabolites:
• Are involved in growth, development, and
reproduction of the organism.
• Formed during the growth phase (Log phase)
• Examples: alcohols such as ethanol, lactic
acid, vitamins and certain amino acids.
 Secondary metabolites:
• Do not play a role in growth, development,
and reproduction like 1ry metabolites do.
• Many have a role in ecological function,
including defense mechanisms, by serving as
antibiotics and by producing pigments.
• Typically formed during the end or near the
stationary phase of growth.
 Secondary
metabolites

Primary
metabolites
Negative feed back inhibition:
The biochemistry of cells relies on a sequence of
enzymes arranged in a metabolic pathway.
End-product inhibition (or feedback inhibition) is a
form of negative feedback by which metabolic
pathways can be controlled
Biotechnologists seek to understand
these regulatory mechanisms and exploit
them, modify the normal metabolism of the
cell, so that the particular product required
is made in maximum amounts:
- Example: Yeast can metabolize
glucose along two alternative
pathways to produce either glycerol
or ethanol:
- If sulphite is added, this will
combine with the ethanal
(acetaldehyde), blocking the ethanol
pathway, so more glycerol is
produced.
- This process was used by the Germans
to produce glycerol in the First World
War to make a number of
explosives such as nitroglycerine.
 There are various fermentation pathways in different
microorganisms. These can be used to produce a range of
alcohols and organic solvents e.g.:
The cell's DNA can be altered to achieve
certain required product by:
A- Screening microorganisms and
selecting those with the best qualities.

B- Mutation induction and favorable

mutations are detected by screening
procedures.

C- Genetic engineering (A more reliable,

modern method), whereby the required gene
is inserted in the cell's genome.
Fermentation
Fermentation technology:
Definition & Development phases:
Is an important component of most “old‟ and
“new‟ biotechnology processes and will
normally involve complete living cells
(microbe, mammalian or plant), organelles
or enzymes as the biocatalyst, and will aim
to bring about specific chemical and/or
physical changes in biochemical materials
derived from the medium.
Historical phases for the use of
industrial microorganisms:
A. Traditional industrial microbiology.
B. Modern industrial fermentations.
C. Recombinant DNA technology
(Modern biotechnology).
a)Traditional industrial microbiology:
Existed for thousands of years,
e.g. preserving milk and vegetables, and
yielding products such as bread, beer,
wine, distilled spirits, vinegar, cheese.
b) Modern industrial fermentations:
• Began in the early 20th century.
• This golden era of industrial fermentation featured
the first large scale fermentations devoted to
manufacture of solvents, organic acids,
vitamins, enzymes, and other products.
• In mid-century, antibiotic fermentations came on
the scene with the development of processes for the
production of penicillin and streptomycin.
• To a new field of biochemical (microbiological)
engineering. On the heels of this major development
was the academic development of mutational
microbial genetics which was developed into a new
technology of strain improvement.
c) Recombinant DNA technology
(Modern biotechnology):
• It began in the early seventies after many
years of discoveries in basic genetics.
• The recombinant DNA developments
made in 1972 in the laboratories of
Stanford University and the University of
California at San Francisco propelled the
field to new heights and led to the
establishment of a new biotechnology
industry in the U.S. and around the world.
The advantages of using microorganisms in
biotechnology:
(i) A high ratio of surface area to volume, which
facilitates the rapid uptake of nutrients required
to support high rates of metabolism and
biosynthesis.
(ii) A wide variety of reactions that
microorganisms are capable of carrying out
(iii) Facility to adapt to a large array of different
environments, allowing a culture to be
transplanted from nature to the laboratory
flask or the factory fermenter, where it is capable
of growing on inexpensive carbon and nitrogen
sources and producing valuable compounds
(iv) Ease of genetic manipulation, both in
vivo and in vitro, to increase production up
to thousands-fold, to modify structures and
activities, and to make entirely new products.
(v) Simplicity of screening procedures
allowing thousands of cultures to be examined
in a reasonably short time.
(vi) A wide diversity, in which different
species produce somewhat different enzymes
catalyzing the same reaction, allowing one
flexibility with respect to operating conditions
in the reactor.
** Microbial products may be very large
materials such as proteins, nucleic acids,
carbohydrate polymers, or even cells, or
they can be smaller molecules which we
usually divide into metabolites essential for
vegetative growth (primary metabolites)
and that inessential (secondary
metabolites).
Methods of Fermentation:
Definition of fermentation:
The growth of large quantities of
cells under aerobic or anaerobic
conditions, within a vessel referred to as
shake flask or fermenter (bioreactor)
to obtain certain product of value.
Solid substrate fermentation:
• Oldest method of
fermentation, and involves
growing microorganisms on a
solid or semi-solid
substrate.
• Examples: Growing
mushrooms on compost,
bread making, cheese
production, sauerkraut.
• Non-food examples include
methanogenesis from
sewage, sludge and other
waste.
Aqueous fermentation:
o It includes: Batch and continuous fermentation
Fermenters
(Bioreactor)
Typical requirements of bioreactor: (Inlets and
outlets, valves)
1. The vessel should be strong
enough to withstand the
various treatments such as
exposure to high heat,
pressure and strong
chemicals and washings.
2. The vessel should be able to
be sterilized and to
maintain stringent
aseptic conditions over
long periods of the actual
fermentation process.
3. The vessel should be
equipped with stirrer or
mixer or agitator or impeller
to ensure distribution of
nutrients, oxygen, and
microbial cell mass in the
fermenter.

4. It should have sensors

(probes) controlling pH,
oxygen level, and
temperature to monitor and
control the fermentation
process.
5. It should be
provided with
inoculation point
for aseptic transfer in
inoculum.

6. Sampling outlets
for withdrawing a
sample for different
tests.
7. Baffles should be provided in
case of stirred fermenter to
prevent vortex formation.
8. It should be provided with
facility for intermittent addition
of an antifoam agent e.g.
silicone oil, polyglycols
what is the problem with foam???

Foaming reduces the productive

volume, i.e. increasing process
costs, and can lead to blockage of
the outlets and threat the
sterility of a fermenter.
9. In case of aerobic
submerged fermentation,
the tank should be
equipped with the
aerating device.
10. Provision for
controlling temperature
and pH of fermentation
medium.