Enhanced artemisinin production by cell cultures of Artemisia annua

Artemisinin, an endoperoxide containing sesquiterpene lactone from Artemisia annua, has proven very effective in treating drug resistant cases of malaria and cancer. To counter the present low content in leaves and uneconomical chemical synthesis, alternate ways to produce artemisinin have been sought. Inspite of extensive work in this area, artemisinin remains elusive in dedifferentiated and differentiated cultures of A. annua. This work reports the first successful approach for production of artemisinin by cell cultures of A. annua cultures of Indian variety of A. annua. Various precursors of terpenoid biosynthesis by isoprenoid pathway were incorporated to study their influence on artemisinin biosynthesis. Artemisinin content was maximally increased by 2.0 times, in comparison to control, when mevalonic acid (50 mg/L) was added as precursor. Various biotic and abiotic elicitors were also tested at different concentration. A maximum increase of 3.47 times in artemisinin accumulation was attained when methyl jasmonate (5 mg/L) was added. Based on these results, an integrated bioprocess for productivity enhancement of artemisinin was developed. A maximum artemisinin accumulation of 96.8 mg/L artemisinin was produced on supplementation of mevalonic acid and methyl jasmonate as selected precursor and elicitor respectively, which was 4.79 times higher in productivity than control callus cultures (20.2 mg/L).