1021-4437/05/5201- © 2005
Russian Journal of Plant Physiology, Vol. 52, No. 1, 2005, pp. 58–62. From Fiziologiya Rastenii, Vol. 52, No. 1, 2005, pp. 68–73.
Original English Text Copyright © 2005 by Zhang, Ye, Liu, Wang, Li.
Artemisinin, an endoperoxide lactone, is currently
the new potent antimalarial drug . Due to expensive
chemical synthesis of artemisinin, its extracting from
plants is the only reliable resource . In
plants, the highest content of artemisinin was
described before ﬂowering , whereas some authors
observed it at full blooming [4–6]. To elucidate the rela-
tionship between artemisinin accumulation and ﬂower-
ing, we studied the mechanism how ﬂowering induces
, a phytohormone inducing ﬂowering, most
probably activates the induction of artemisinin produc-
tion in the ﬂowering plant. The increase in artemisinin
content was found in the GA
-treated shoot cultures .
But no explanation was received. It is well known that
the biosynthetic pathways of gibberellins and artemisi-
nin are the same before farnesyl pyrophosphate (FPP).
After FPP, the isoprenoid pathway is directed to arte-
misinin production by amorpha-4,11-diene synthase (a
sesquiterpene synthase) that catalyses probably the ﬁrst
step in artemisinin biosynthesis , whereas gibberel-
lin biosynthesis starts by GGPP synthase and diterpene
synthase (Fig. 1). We assumed that the feedback effect
of the exogenous GA
might result in carbon diverting
into the artemisinin production resulting in an increase
in the artemisinin content.
It was shown that the content of artemisinic acid, a
precursor in the biosynthesis of artemisinin, was 8–
10 times higher than that of artemisinin in
10], but an opposite observation was also reported .
treatment and ﬂowering stimulated artemisinin
shoot cultures and plants,
respectively; however, there were no reports on the con-
tent variation of artemisinic acid in these plants.
Here, the contents of artemisinic acid and artemisi-
nin were measured in
001 strain vegetative
plants treated with GA
at different developmental
stages. Moreover, the endogenous GA
also estimated. In order to test whether the feedback
inhibition of GA
may result in carbon ﬂow diversion to
the artemisinin production via the isoprenoid pathway,
we have studied the amorpha-4,11-diene synthase gene
transcription pattern in the vegetative plants treated by
MATERIALS AND METHODS
strain from Sichuan Province, China, were planted into
soil under 16/8 h light/dark cycles at 25
C and an
illuminance of 3000 lx.
74-day-old plants were transplanted
into sterilized pure sand and grown under the same con-
ditions. They were watered every other day and fertil-
ized with Hoagland solution twice a week. After two
weeks, the plants, which were still at the vegetative
and Flowering Induce the Conversion
of Artemisinic Acid to Artemisinin in
Y. S. Zhang, H. C. Ye, B. Y. Liu, H. Wang, and G. F. Li
Key Laboratory of Photosynthesis and Environmental Molecular Physiology, Institute of Botany,
Chinese Academy of Sciences, Beijing, 100093 China;
fax: 86-10-82-59-1016; e-mail: firstname.lastname@example.org
Received April 29, 2004
—The contents of artemisinin and artemisinic acid were monitored in the
treated with GA
at vegetative and ﬂowering initiation stages
The highest artemisinin content was observed at
full bloom. The decrease in artemisinic acid content occurred during the transition from the vegetative stage to
the beginning of ﬂowering. Endogenous GA
content in the leaves peaked at full bloom. At the vegetative stage,
in plants treated with various concentrations of GA
, the content of artemisinin increased while that of arte-
misinic acid decreased. Apparently, the rate-limiting step in artemisinin biosynthesis was from artemisinic acid
to artemisinin. The “bottleneck” of artemisinin biosynthesis was probably unlocked during the ﬂowering or in
the vegetative plants treated with GA
, which triggered off the conversion of artemisinic acid to artemisinin.
Key words: Artemisia annua - artemisinin - artemisinic acid - amorpha-4,11-diene synthase - GA
ment - ﬂowering
: DMAPP—dimethylallyl pyrophosphate; FPP—
farnesyl pyrophosphate; GA
—gibberellic acid; GGPP—geranyl
geranyl pyrophosphate; GPP—geranyl pyrophosphate; IPP—iso-
pentenyl pyrophosphate; PCR—polymerase chain reaction.
This article was presented by the authors in English.