Bio 417

L20 2022

Potential of Biotechnology to tackle Malaria…

1
Malaria
A global health problem
90% of the cases occur in Africa
In 2020, this disease killed 500 000
children under 5yrs in Africa!
this disease is transmitted by Anopheles
mosquitoes that feed on human blood

In Botswana, this disease is largely caused by Plasmodium

falciparum and to a lessor extent, Plasmodium vivax
Quinine drugs were used to treat malaria over many years
Consequently, resistance to these drugs developed and
more so in malaria endemic areas
Currently, primaquine is among the best drugs against
Plasmodium gametocytes
But, it can induce haemolysis in Glucose 6-phosphate
dehydrogenase (G6PDH) deficient individuals
this together with the high doses required
for treatment of P. vivax infections makes it
less attractive
Presently, the WHO chosen treatment comprises combination
of artemisinin and or its derivatives; dihydroartemisinin,
artemether, and artesunate
the current and very common practice is to use
artemisinin in combination with another drug
This is what has become known as Artemisinin-combination therapy
The treatment regimen is characterised by;
rapid onset of action
quick elimination
favourable safety and tolerability
Artemisinin is a natural product from some members of the family
Asteraceae
it is a sesquiterpene lactone with efficacy against malaria
parasites
it specifically and selectively inhibits the sarco/endoplasmic
reticulum Ca2+ ATPase of P. falciparum after activation by ionic
forms of iron
(Wei Wen and Rongmin Yu (2011 In: Pharmacognosy Reviews 5(10):
189-
The present day well known Artemisinin source is the plant
Artemisia. annua
But the yield is very low (0.01-0.5%) per dry weight of plant tissue
Whereas,
malaria affects far too many people
children under 5 years are the most vulnerable
This is clearly a burden on health care
systems!

But the most pressing aspect is the inadequate product

yield by A. annua and the associated prospect of plant
extinction!

This calls for deliberate efforts to explore alternative means of

producing artemisinin

Can Biotechnology help?????

Please Participate!
What will it take for Biotechnology to contribute to this
important human welfare call?
Please Participate!
Knowledge of what influences the activation /
de-activation of all enzymes in the pathway of
artemisinin biosynthesis
Evaluation of the most critical ex-situ method of
production

Biosynthesis of artemisinin begins at farnesyl

pyrophosphate step in the Mevalonic acid biosynthesis
pathway
The Mevalonic acid biosynthesis pathway
What next if we know the pathway?

Engineering the host to overexpress enzymes leading to desirable

product yield

Elucidation the most suitable feedstock for Acetyl-CoA

If the host is yeast, a choice between ethanol and
glucose

What are the other likely challenges that must be overcome?

catabolite repression
this informs feedstock choice
Please READ:
Kung et al. (2018): Frontiers in Plant Science
doi: 10.3389/fpls.2018.00087
Also READ:
Muangphrom et al (2016) J Nat Med (2016)
70:318-