As the world geared itself to commemorate World Malaria Day on 25 April, systems biologists at the CSIR were preparing to wrap up the first phase of a research project that could have a profound effect on the antimalarial pharmaceutical industry in coming years.
Mulalo Nemutanzhela, a plant biotechnologist, investigates transforming the protein profile of the African species of the artemesia plant to enable it to produce artemisinin, a powerful antimalarial compound. She recently visited the CSIR's Japanese partners to discuss further collaboration
For the past two years the CSIR, in collaboration with Riken - a top Japanese scientific research institution - has been investigating the possibility of engineering the production of artemisinin, a powerful antimalarial compound, in an indigenous African shrub.
Artemisinin occurs naturally in the Asian plant, Artemesia annua, but has never been recorded in its sister species Artemesia afra, which can be found in some regions of southern Africa, East Africa and Ethiopia. Known as wilde als, Africa wormwood, umhlonyane or lengana in South Africa, the plant is commonly found in the Cedarberg mountains in the Cape.
Artemisinin, used in traditional Chinese medicine for over 2 000 years, is the most promising drug for quinoline-resistant malaria parasites. The use of artemisinin-based combined therapies for malaria patients has been recommended by the World Health Organization. The species indigenous to South Africa has been used to treat coughs, colds, influenza and is said to relieve menstrual cramps and pain after giving birth. Fresh leaves from this shrub can also be used to treat tooth ache and relieve gum infections.
"The two species are related in terms of their molecular biology," explains Dr Dalu Mancama, who heads the CSIR's systems biology research group. "What we want to know is whether it would be possible to modify certain traits in Artemesia afra, allowing it to produce artemisinin or a similar compound. Tests have shown that it doesn't contain this compound but precursor qualifiers similar to those found in its Asian relative exist."
Worldwide, artemisinin is regarded as a prized antimalarial compound and with its primary source occurring in Asia, is very expensive due to its scarcity. "One of the challenges with artemesia is that you need lots of land to grow large amounts of the plant and harvest sufficient quantities of artemisinin. The amount of artemisinin you get from an adult plant is very little, between 0,01 and 1% of the dry weight of a single plant. This makes the resulting compound expensive." explains Mancama.
For this reason the CSIR and Japanese teams are motivated to stimulate the production of the compound in the African species. Mancama's team is focusing on identifying molecular differences between the two species and determining the feasibility of developing plant biotechnology protocols for transforming the A. afra plant into an artemisin-producing variant. They have not yet developed a genetically-modified African plant.
The Japanese, led by Professor Toshiya Muranaka of the Riken Plant Science Centre, have contributed molecular knowledge on the Asian artemesia plant and the particular enzymes missing in the African species.
The collaboration resulted from a meeting held at the CSIR in 2004 to exploit a bilateral agreement between the governments of Japan and South Africa. The aim was to identify means of adding value to South African indigenous plants to aid in combating infectious disease. The project is sponsored by the National Research Foundation and the Japanese equivalent, the Japan Science and Technology Agency.
The research team is expected to present its final report in May on completion of the first phase. Recently a CSIR representative visited Japan to discuss furthering the collaboration. "The Japanese expressed a keen interest in our proteomics capabilities," reveals Mancama. "They do much gene-based work but not in proteomics, so for them that's an interesting angle. One of the limiting factors of using proteomics is that the required equipment is very expensive - CSIR bioscientists are in a fortunate position to have such equipment."