Seasonal Variation of Artemisinin and its Biosynthetic Precursors in Plants of Artemisia annua of Different Geographical Origin: Proof for the Existence of Chemotypes (original) (raw)

Planta Med 2000; 66(1): 57-62
DOI: 10.1055/s-2000-11115

Original Paper

Georg Thieme Verlag Stuttgart · New York

• Department of Pharmaceutical Biology, University Centre for Pharmacy, Groningen Institute for Drug Studies, University of Groningen, Groningen, The Netherlands

Further Information

Publication History

Publication Date:
31 December 2000 (online)

Abstract

The time course of the levels of artemisinin, its biosynthetic precursors and the biosynthetically related sesquiterpenes was monitored during a vegetation period of Artemisia annua plants of different geographical origin. Considerable differences in contents of artemisinin and its direct precursors artemisinic acid and dihydroartemisinic acid were found between these A. annua's. For the first time the A. annua plants of different geographical origin were found to belong to different chemotypes. A chemotype with a high artemisinin level was found to have also a high dihydroartemisinic acid level but a relatively low artemisinic acid level. Reversibly, a chemotype with low levels of artemisinin and dihydroartemisinic acid contained a high artemisinic acid level. Artemisinic acid is considered to be the direct precursor of dihydroartemisinic acid in the biosynthetic pathway of artemisinin. The observed accumulation of artemisinic acid in one of the A. annua chemotypes may indicate the presence of a rate-limiting step in the biosynthetic pathway of artemisinin. The enzymatic reduction of artemisinic acid into dihydroartemisinic acid is probably a „bottle neck” in the biosynthetic pathway of artemisinin in varieties with high artemisinic acid and consequentially low artemisinin levels. After a night-frost period, the level of artemisinin was increased, in the Vietnamese A. annua plants, while the dihydroartemisinic acid level was decreased. This phenomenon is in accordance with our hypothesis that stress triggers the conversion of dihydroartemisinic acid to artemisinin. It is suggested that the presence of high levels of dihydroartemisinic acid may be an adaptation to stress conditions (e.g., night-frost), during which relatively high levels of 1O2 are formed. Dihydroartemisinic acid gives the plant protection by reacting with these reactive oxygen species yielding artemisinin as stable end-product.

Key words

Artemisia annua L. (Asteraceae) - artemisinin, artemisinic acid reductase - biosynthetic pathway - dihydroartemisinic acid - chemotypes

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Dr. N. Pras

Department of Pharmaceutical Biology

University Centre for Pharmacy

University of Groningen

A. Deusinglaan 1

NL-9713 AV Groningen

The Netherlands

Email: N. Pras@farm.RUG.NL

Phone: +31 50 3637570

Fax: +31 50 3633299