Heterologous Biosynthesis of Artemisinin in <i>Chrysanthemum morifolium</i> Ramat

Artemisinin-based drugs are the most effective medicine against multidrug-resistant <i>Plasmodium</i> spp., the parasite that causes malaria. To this day, wormwood <i>A. annua</i> L. is the sole commercial source of artemisinin, where it is produced in minor amounts. The arte...

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Main Authors: Aleksey Firsov, Alexander Pushin, Svetlana Motyleva, Svetlana Pigoleva, Lyubov Shaloiko, Alexander Vainstein, Sergey Dolgov
Format: Article
Language:English
Published: MDPI AG 2021-05-01
Series:Separations
Subjects:
Online Access:https://www.mdpi.com/2297-8739/8/6/75
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author Aleksey Firsov
Alexander Pushin
Svetlana Motyleva
Svetlana Pigoleva
Lyubov Shaloiko
Alexander Vainstein
Sergey Dolgov
author_facet Aleksey Firsov
Alexander Pushin
Svetlana Motyleva
Svetlana Pigoleva
Lyubov Shaloiko
Alexander Vainstein
Sergey Dolgov
author_sort Aleksey Firsov
collection DOAJ
description Artemisinin-based drugs are the most effective medicine against multidrug-resistant <i>Plasmodium</i> spp., the parasite that causes malaria. To this day, wormwood <i>A. annua</i> 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 <i>Chrysanthemum morifolium</i> Ramat. (<i>C. morifolium</i> 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.
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spelling doaj.art-b32623d004a54c298f50de8b1a76f28a2023-11-21T21:52:11ZengMDPI AGSeparations2297-87392021-05-01867510.3390/separations8060075Heterologous Biosynthesis of Artemisinin in <i>Chrysanthemum morifolium</i> RamatAleksey Firsov0Alexander Pushin1Svetlana Motyleva2Svetlana Pigoleva3Lyubov Shaloiko4Alexander Vainstein5Sergey Dolgov6Branch of the Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry of the Russian Academy of Sciences, Prospekt Nauki, 6, Pushchino, 142290 Moscow Region, RussiaBranch of the Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry of the Russian Academy of Sciences, Prospekt Nauki, 6, Pushchino, 142290 Moscow Region, RussiaFederal Scientific Selection and Technology Center for Horticulture and Nursery, Zagoryevskaya St. 4, 115598 Moscow, RussiaBranch of the Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry of the Russian Academy of Sciences, Prospekt Nauki, 6, Pushchino, 142290 Moscow Region, RussiaBranch of the Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry of the Russian Academy of Sciences, Prospekt Nauki, 6, Pushchino, 142290 Moscow Region, RussiaRobert H. Smith Faculty of Agriculture, Food and Environment, The Hebrew University of Jerusalem, POB 12, Rehovot 76100, IsraelBranch of the Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry of the Russian Academy of Sciences, Prospekt Nauki, 6, Pushchino, 142290 Moscow Region, RussiaArtemisinin-based drugs are the most effective medicine against multidrug-resistant <i>Plasmodium</i> spp., the parasite that causes malaria. To this day, wormwood <i>A. annua</i> 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 <i>Chrysanthemum morifolium</i> Ramat. (<i>C. morifolium</i> 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.https://www.mdpi.com/2297-8739/8/6/75plant biotechnologymalariaheterologous biosynthesisartemisinin<i>Chrysanthemum morifolium</i>plant metabolic engineering
spellingShingle Aleksey Firsov
Alexander Pushin
Svetlana Motyleva
Svetlana Pigoleva
Lyubov Shaloiko
Alexander Vainstein
Sergey Dolgov
Heterologous Biosynthesis of Artemisinin in <i>Chrysanthemum morifolium</i> Ramat
Separations
plant biotechnology
malaria
heterologous biosynthesis
artemisinin
<i>Chrysanthemum morifolium</i>
plant metabolic engineering
title Heterologous Biosynthesis of Artemisinin in <i>Chrysanthemum morifolium</i> Ramat
title_full Heterologous Biosynthesis of Artemisinin in <i>Chrysanthemum morifolium</i> Ramat
title_fullStr Heterologous Biosynthesis of Artemisinin in <i>Chrysanthemum morifolium</i> Ramat
title_full_unstemmed Heterologous Biosynthesis of Artemisinin in <i>Chrysanthemum morifolium</i> Ramat
title_short Heterologous Biosynthesis of Artemisinin in <i>Chrysanthemum morifolium</i> Ramat
title_sort heterologous biosynthesis of artemisinin in i chrysanthemum morifolium i ramat
topic plant biotechnology
malaria
heterologous biosynthesis
artemisinin
<i>Chrysanthemum morifolium</i>
plant metabolic engineering
url https://www.mdpi.com/2297-8739/8/6/75
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