Effect of dimethyl-beta-cyclodextrins on artemisinin production in Artemisia annua suspension cell cultures.

Abstract

Artemisinin is an effective antimalarial compound obtained by thè aerial parts of thè herbalplant Artemisia annua L. Unfortunately, thè production of artemisinin in plants is very low (0.1-1% on a dry weight basis) and its chemical synthesis is very difficult. In recent yearsbiotechnological attempts to improve artemisinin production either in plant or geneticallyengineered microrganisms were made. A. annua celi and tissue cultures were also exploredfor thè production of artemisinin, although thè yieids obtained have been so far quite low. Wehave recently established A. annua celi cultures able to biosynthesize artemisinin and torespond to thè elicitation by methyl jasmonate (MeJA). Interestingly, amounts of artemisininproduced by these cultures were also found in thè spent culture medium. Cyclodextrins (CDs)are known to increase thè water solubility of various compounds, by forming host-guestinclusion complexes. Chemically modified CDs, such as 2,6 dimethyl-p-cyclodextrins (DIMEB)have been successfully used to improve thè production of health-promoting plant metabolitessuch as resveratrol in grape celi cultures. The aim of this work was to evaluate thè ability ofDIMEB to enhance artemisinin production in A. annua suspension celi cultures. HPLCanalysis of artemisinin and Real Time PCR gene expression analysis were carried out inDIMEB treated and untreated cultures. DIMEB induced a 300-fold increase of artemisininlevels in thè spent culture medium after a three-day-treatment. The addition of MeJA induceda further increase of thè artemisinin amounts. The expression levels of artemisininbiosynthetic genes (cytochrome P450 monoxygenase, cytochrome P450 reductase andartemisinic aldehyde A11 reductase) were not altered by thè DIMEB treatment. These resultssuggest that DIMEB improved artemisinin yieids of A. annua celi cultures, probably notaffecting thè biosynthetic pathway but enhancing thè solubility and stability of artemisininmolecules.


Tutti gli autori

  • Durante M.; Quarta A.; Nisi R.; De Paolis A.; Mita G.; Caretto S.

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Anno di pubblicazione

2010

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