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Summary Biotechnology 2 (FHM-31806)

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In this summary all lectures and the accompanying background information of the course Biotechnology 2 (FHM-31806), which is given as obligatory part of the Bachelor's degree program in Biotechnology at Wageningen University, are included. Thus, this summary provides a complete overview of the exam...

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  • May 4, 2018
  • May 9, 2018
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Summary Lectures + Background information Biotechnology 2
Lecture 1 – Introduction
Biotechnology: application of organisms or parts of organisms in technical processes.

2 types of classifications of biotechnology exist:
1. Classification in generations.
2. Classification in types of industries.

Generations of biotechnology:
1. Traditional/classic biotechnology: biotechnology which was used for centuries to produce food
products like beer, cheese, bread and soy sauce. -> people had no idea why it worked, they knew
only that it did work.
2. Industrial biotechnology: biotechnology which produces on industrial scale products like
antibiotics, amino acids, citrate, acetone and butanol. -> people knew that a microorganism was
responsible for the process + people used the wild type microorganism (no gene technology present
yet).
3. Modern biotechnology: biotechnology in which gene technology is applied on organisms to
produce products like pharmaceutics (e.g. human insulin), (industrial) enzymes, fine chemicals, food
and detergents.

Advantage of modern biotechnology = the use of genetically modified organisms in processes lowers
the costs of these processes by lowering the most important factors which determine the costs of a
process:
- The amount of raw material(s) needed.
- The amount of water and steam needed.
- The amount of electricity needed.

Main hurdles for use of modern biotechnology on large scale:
- Acceptance (e.g. many people still prefer food for which no genetic modification was used during
production).
- Regulation -> approval of products developed with modern biotechnology often takes a lot of time
and money.

Different types of biotechnological industries, each indicated with a different colour:
1. Red biotechnology = medical biotechnology: biotechnology which develops products for
healthcare.
2. Green biotechnology = agricultural biotechnology: biotechnology in which food and other
agricultural products (e.g. rapeseed oil) are developed.
3. Blue biotechnology:
- Marine biotechnology: biotechnology which focusses on fish and other marine organisms.
- Environmental biotechnology: biotechnology which aims at getting rid of pollution of the
environment by cleaning air, water and soil.
4. White biotechnology = biobased technology: biotechnology which aims at saving the environment
by replacing petrochemical compounds (compounds derived from fossil fuels) in production lines by
compounds which are renewable because they are biobased (made from biomass).
- Industry which has a slow but constant growth at the moment.
- Mainly aims at using agricultural (by-)products -> sugars and/or amino acids out of these converted
to the main products of biobased technology:
a. Biochemicals (e.g. food ingredients, pharmaceuticals, fine chemicals).

,b. Biomaterials (e.g. polymers).
c. Biofuels (e.g. ethanol, hydrogen gas).
d. Sustainable energy
- Ultimate goal is to establish biobased economy: economy which is circular because all products are
biobased (made from biomass) and thus made of renewable compounds.




Driving forces of the white biotechnology/biobased technology:
- Sustainability
- The need of securing the (future) supply of raw materials.
- The need of securing the (future) supply of energy. -> increasing world population + increasing
welfare lead to higher and higher energy demand.
- Consumer behaviour -> most consumers prefer biobased products over other products.
- High prices of fossil fuels.

Barriers/hurdles for the white biotechnology/biobased technology:
1. Technical barriers/hurdles:
- Biomass availability
- Storage and transport -> biomass occupies in general more space than petrochemical compounds
because biomass usually contains a lot of water.
2. Economic barriers/hurdles:
- Price regime of the agricultural policy.
3. Political and legal barriers/hurdles:
- Intellectual property -> when someone has a good idea in the white biotechnology/biobased
technology often no other people may use it because of intellectual property, so development is not
sped up.
- Regulation:
a. Regulation is necessary to favour biobased products to speed up their use and development.
b. Currently not much regulation for biobased products exists, so a lot of regulation is necessary for
new biobased products. -> uncertainty about what will be permitted and what will not be permitted
slows down the development of new biobased products.
4. Social barriers/hurdles:

,- Competition with food -> biobased products from which the production competes with food
production are not favoured by society.

Sustainability is determined by the Triple-P bottom line (People, Planet, Profit): guideline which
states that something is sustainable if it is:
- Socially responsible (People) One of those requirements for sustainability is
- Environmentally sound (Planet) NOT met? -> NOT sustainable!
- Economically feasible (Profit)

Feasibility of biotechnological process is determined by:
- Non-technical factors
- Technical factors

First and most important step for determining feasibility of a process, which thus always should be
executed before you start designing the process = compare the market value of the substrate which
is used in the process with the market value of the product of the process:
a. Market value product < market value substrate -> process definitely NOT feasible!
b. Market value product > market value substrate -> process could be feasible.

The non-technical factors which determine the feasibility of a biotechnological process:
1. Market: is there a lot of demand for the product which is produced in the biotechnological
process? If yes, profit can be made using the biotechnological process and it thus has a higher
feasibility.
2. Politics/policy: laws and regulation determine feasibility of a biotechnological process, when the
biotechnological process is for example permitted it will be a lot more feasible.
3. Competition: the better the biotechnological process can compete with other processes which
produce the same product, the more feasible the biotechnological process is. -> how good process
can compete with other processes is determined by the following factors:
- Availability of the substrate:
a. The higher the availability of the substrate, the lower its price and the better the process can
compete.
b. A substrate which cannot be used as food will have a higher availability and is therefore preferred.
- Price-volume relation of the product: the higher the price you can ask for the product and the
higher the volume in which it is produced, the better the process can compete.
- Purity of product/concentration of product in water: the higher the purity of the product (higher
concentration in water), the higher the price you can ask for your product and the better the process
thus can compete.
5. Sustainability: the more sustainable the process is, the more feasible the process is.
E.g. Production of CO2: the less CO2 is emitted in the process, the better the process is for the
environment, the better the process can compete.
6. Social acceptance: the better the process is accepted by society, the more people will be in favour
of the process and the more feasible the process is.
7. Consumer behaviour: the more added-value the product of the process has, the more consumers
will favour the product of the process and the more feasible the process is.
8. Intellectual property: the less intellectual property of others is needed for the process, the more
feasible the process is.

, Lecture 2 – Technical feasibility
Steps in designing a biotechnological production process:
1. Product -> which product do you want to produce?
2. Host -> which organism is used to produce the product?
3. Construct -> how are you going to modify the host (creating a construct out of the
host)?
4. Cultivation -> how are you going to cultivate the construct?
5. Down Stream Processing (DSP) -> how are you going to purify the produced
product?
6. Formulation -> in which form are you going to sell the product (e.g. as a pill, as a
powder etc.)?

Design criteria for the host:
1. Production: the higher the production level of the host, the more suitable the host is for the
process. -> production level of host can be increased by (genetically) modifying the host. -> picking a
host which is closely related to the donor organism will in general result in a higher production level
than picking a host which is (almost) not related to the donor organism.
2. Safety: the safer the host is, the more suitable the host is for the process.
a. A host is safer if it:
- Produces no virulence factors.
- Produces no toxins (can nowadays easily be seen by looking at its genome).
- Produces only products with the GRAS (generally recognised as safe) status. -> E.g. food grade
organisms (organisms which are used in food production).
b. The less safe the host is, the more time and money has to be invested to get the use of the host in
the process legislated. -> use of host which is not safe at all often unwanted.
c. Importance of safety of the host differs for different applications of the product:
- Medical application of product? -> safety host = less important -> for medical applications safety is
ensured by the long trial studies necessary to get the product on the market + estimated revenue is
quite high which makes the use of a lot of time and money to get the host legislated worth the try.
- Food application of product? -> safety host = more important
3. Knowledge: the more knowledge there is over a host, the better picking this host for the process is
and thus the more suitable the host for the process is.
- Hosts with which there is experience in past large scale processes are preferred.
- Knowledge about cultivation conditions and fermentation behaviour is particularly important.
- Host which is a so-called PLUGBUG system is preferred. -> PLUGBUG system: host which has been
modified in such a way that a desired modification can easily be plugged into this host (with e.g.
CRISPR CAS).
4. Post-translational processes: the better the post-translational processes in the host are in creating
the right protein folding, the more suitable the host is for the process.
a. Post-translational processes can be necessary for:
- Protein folding
- Secretion
b. If post-translational processes create the exact correct protein folding is in general only relevant
when products with medical applications (e.g. pharmaceuticals) are produced in the process,
because then the exact three-dimensional structure is really important for creating the right
interactions in a patient’s body, because not exactly the right interactions can lead to unwanted side-
effects. -> the so-called “substantial equivalence” (the more closely a medical product resembles its
natural equivalent, the higher the substantial equivalence of the product) is really important for a

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