[BIO8041]
In-course MCQ question
1.
Which of the following best describes a biosynthetic gene cluster the product
from which can be structurally predicted, but as yet been no product has been
isolated?
a.
silent
b.
non-ribosomal
c.
cryptic
d.
epigenetic
2.
Coelichelin, a natural product, discovered by genome mining is encoded by a:
a.
Siderophore lyase.
b.
Type-II polyketide synthase
c.
Type-I polyketide synthase
d.
Non-ribosomal peptide synthetase
3.
Which of the following best describes the use of intact bacteriophage to treat
microbial infection
a.
Phage therapy
b.
Phagocytosis
c.
Phagicide
d.
Phage-derived therapy
4.
Which of the following antimicrobial compounds was discovered through the
use of bacterial antisense RNA methodology?
a.
Cerulenin.
b.
Berberine.
c.
Platensimycin.
d.
Cephalosporin.
5.
How does antisense Peptide Nucleic Acid (PNA) silence translation of a gene
to which it is targeted?
a.
RNAse-III mediated digestion of the PNA-mRNA duplex.
b.
Post-translation modification of the peptide.
c.
Steric hinderance of the ribosome.
d.
All of the above.
Exam questions
1.
In terms of drug discovery, what is ADME/T?
ADME/T stands for adsorption, distribution, metabolism, excretion and toxicity.
These are properties that are related to the pharmacokinetics of a drug. These
are the properties of a drug as they relate to its presence in humans. Drug
discovery may start with finding a hit for a specific target, but screening is not
conducted in the system (human body) for which it is intended. For a hit to make
it to a marketable drug, it must not have side effects that outweigh its benefits.
[BIO8041]
This is where ADME/T studies are relevant. Understanding the fate of a
compound in humans (or mammal models) is essential to understand the risks of
that compound e.g. a potential drug may treat its condition but accumulate in
the kidneys and be broken down in to a toxic metabolite that ultimately destroys
kidney function. Thus, predictions can be made based on ADME/T as to whether
a potential drug will make it to market. Alternatively, ADME/T may provide a
means to change the drug profile (e.g. topical as opposed to oral application) or
be used to alter the chemistry of the potential drug to ensure that it will pass
clinical trials.
2.
Describe, using examples, how synthetic biology can be used to improve the
production of natural-product drugs that are currently extracted directly from
the producing organism.
Synthetic biology is the use of standardised genetic parts to enable the use of
engineering principals to build new genetic systems. It is of particular interest in
the area of natural product synthesis, especially in the production of high value
drugs. Natural products derived from plants, microbes or sponges are often only
extracted in minute quantities as a proportion of the biomass. Thus, huge
biological resources are required to obtain enough drug to treat a diseased
population. Purification of natural products from some sources (plants) is often
expensive and difficult; product is often impure after first rounds of purification.
The result of this is that there is often a shortage of the drug and/or it is highly
expensive. Synthetic biology offers the promise of producing such drugs by
microbial fermentation; resulting in cheap production, easy purification and
considerable reduction of the natural resources. An example is the production of
Artemisinin (anti-malarial). This drug is produced by plants, but in small
quantities and purification is difficult. Identification of the some of the genes
responsible for its biosynthesis has enable cloning into E. coli and subsequent
production of an Artemenisinin precursor. Identification and cloning of other
tailoring genes will enable full fermentation-based production of this drug.
Recently, the Bill and Melinda Gates Foundation granted ca. $40 million to a
project collaboration between academics and Industry to develop synthetic
artemensinin (underlines would be evidence of further reading).