| |
Malaria infects approximately 300 million people worldwide and causes 1-1.5 million’s death every year. The situation has become even more complex over the last few years with the parasites acquiring increasing resistance to the antimalarial drugs. Artemisinin, a sesquiterpene lactone endoperoxide isolated from Artemisia annua L. (Asteraceae, also known as the Chinese herbal “Qinghao”), is the most promising new drug for the treatment of this disease. The recent rapid adoption of this medicament, however, has resulted in shortages in supply and increased prices. Due to structural complexity, chemical synthesis of artemisinin has been proven to be very inefficient and expensive. An approach to enhance the production of artemisinin is through the metabolic engineering of key enzyme(s) and regulatory proteins involved in its biosynthetic pathway. However, despite the tremendous importance, the biosynthetic pathway of artemisinin as well as its regulatory mechanism remains poorly characterized. We propose to apply the cDNA-amplified fragment length polymorphism (AFLP) technology, in combination with targeted metabolite analysis, on jasmonate-elicited hairy root system, to study the metabolism of artemisinin in A. annua. Bioinformatics and comparative genomics approach will also be integrated, to identify novel genes and regulatory elements potentially involved in artemisinin biosynthesis. The results from this research will lead us to a more complete understanding of the biosynthesis and regulation of artemisinin, and ultimately, pave the way for biotechnology avenues to overproduce artemisinin in A. annua to benefit human health.
|
|
