Heterologous Biosynthesis of Artemisinin in <i>Chrysanthemum morifolium</i> Ramat
Aleksey Firsov,
Alexander Pushin,
Svetlana Motyleva,
Svetlana Pigoleva,
Lyubov Shaloiko,
Alexander Vainstein,
Sergey Dolgov
Affiliations
Aleksey Firsov
Branch of the Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry of the Russian Academy of Sciences, Prospekt Nauki, 6, Pushchino, 142290 Moscow Region, Russia
Alexander Pushin
Branch of the Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry of the Russian Academy of Sciences, Prospekt Nauki, 6, Pushchino, 142290 Moscow Region, Russia
Svetlana Motyleva
Federal Scientific Selection and Technology Center for Horticulture and Nursery, Zagoryevskaya St. 4, 115598 Moscow, Russia
Svetlana Pigoleva
Branch of the Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry of the Russian Academy of Sciences, Prospekt Nauki, 6, Pushchino, 142290 Moscow Region, Russia
Lyubov Shaloiko
Branch of the Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry of the Russian Academy of Sciences, Prospekt Nauki, 6, Pushchino, 142290 Moscow Region, Russia
Alexander Vainstein
Robert H. Smith Faculty of Agriculture, Food and Environment, The Hebrew University of Jerusalem, POB 12, Rehovot 76100, Israel
Sergey Dolgov
Branch of the Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry of the Russian Academy of Sciences, Prospekt Nauki, 6, Pushchino, 142290 Moscow Region, Russia
Artemisinin-based drugs are the most effective medicine against multidrug-resistant Plasmodium spp., the parasite that causes malaria. To this day, wormwood A. annua L. is the sole commercial source of artemisinin, where it is produced in minor amounts. The artemisinin yield depends on numerous poorly regulated agricultural factors and the genetic variability of this non-domesticated plant. This has aroused significant interest in the development of heterologous expression platforms for artemisinin production. Previously, we obtained lines of Chrysanthemum morifolium Ramat. (C. morifolium Ramat.), cvs. White Snowdon and Egyptianka, transformed with artemisinin biosynthesis genes. Here, we report the results of an analysis of artemisinin production in transgenic chrysanthemums. Transcription of heterologous amorpha-4,11-diene monooxygenase and cytochrome P450 reductase genes in transgenic lines was confirmed using high-resolution melting analysis. Artemisinin accumulation was detected using GC-MS in White Snowdon plants, but not in Egyptianka ones, thereby demonstrating the possibility of transplanting active artemisinin biosynthetic pathway into chrysanthemum. Ways of increasing its content in producer plants are discussed.
