Amorpha-4,11-diene Synthase

Mercke, P., Bengtsson, M., Bouwmeester, H.J. etal. (2000) Molecular cloning, expression, and characterization of amorpha-4,11 -diene synthase, a key enzyme of artemisinin biosynthesis in Artemisia annua L. Archives of Biochemistry and Biophysics, 381, 173-180. 

WaUaart TE, Bouwmeester HJ, Hille J, Poppinga L, Maijers NCA (2001) Amorpha-4, 11-diene synthase cloning and functional expression of a key enzyme in the biosynthetic pathway of the novel antimalarial drug artemisinin. Planta 212 460-465... 

Amorpha-4,11-diene synthase catalyses the first probable step in artemisinin biosynthesis. Phytochemistry 52 843-854. 

Chang YJ, Song SH, Park SH, Kim SU. (2000) Amorpha-4,11-diene synthase of Artemisia annua cDNA Isolation and bacterial expression of a terpene synthase involved in artemisinin biosynthesis. Arch Biochem Biophys 3S3 178-184. 

The genetic engineering of qinghao (4. annua) has also been paid great attention recently some preliminary results about the early stage of qinghaosu biosynthesis have been reported. For example, amorpha-4,11-diene synthase, an enzyme responsible for the cyclization of farnesyl diphosphate into ring sesquiterpene, has been expressed in Escherichia coli and production of amorpha-4,11-diene (122) was identified. °... 

The first step taken in the biosynthetic pathway of artemisinin was the cyclization of the general mevalonate pathway originated sesquiterpenoid precursor farnesyl diphosphate (FPP) into IS, 6R, 7R, i0it)-amorpha-4,ll-diene by amorpha-4,11-diene synthase (AMDS) (Fig. 4) [6-8]. The crystal structure of this sesquiterpene synthase is not known. From aU plant... 

The three-dimensional structures of three non-plant sesquiterpene synthases reveals a single domain composed entirely of a-hehces and loops despite the low homology on amino acid sequence level [14,16,17]. The secondary elements of 5-epi-aristolochene synthase, a plant sesquiterpene synthase, conform to this pattern with the exception of two domains solely composed of a-helices and loops. It is reasonable, but still a matter of debate, to extrapolate these data to the case of amorpha-4,11-diene synthase, which will probably only display a-hehces and loops once the crystal structme has been solved. 

ADS Amorpha-4,11-diene synthase CYP71AV1 Amorphadtene-12-hydroxylase... 

Notable is as well the impact of methyl jasmonate on the biosynthesis of artemisinin, which regulates as a phytohormone the response of a plant to abiotic or biotic stress (e.g. drought, wind, or attacks from herbivores). In case of sweet wormwood, methyl jasmonate stimulates the expression of amorpha-4,11-diene synthase (ADS) and the cytochrome P450 monooxygenase (CYP71AV1), leading ultimately to an enhanced formation of artemisinin. [464]... 

Fig. 99.1 Proposed biosynthetic pathway of artemisinin in Artemisia annua L. plant. SQS Squalene synthase, ADS amorpha-4,11-diene synthase, FPP Famesyl diphosphate, FPS Famesyl pyrophosphate synthase, GPP Geranyl diphosphate, GPPS Geranyle diphosphate synthase, GS germaciene A synthase, DMAPP Dimethylallyl diphosphate, IPP isopeniraiyl diphosphate, CPS P-caryophyllene synthase, DBR2 double bond reductase 2, ECS epi-cedrol synthase, FPP fanesyl diphosphate, PS (E)-P-famesene synthase (Drawn based on informatitm published by Abdin et al., [18] and Zhang et al., 2005)...

Picaud S, Olofsson L, Brodelius M, Brodelius PE (2005) Expression, purification, and characterization of recombinant amorpha-4,11-diene synthase from Artemisia annua L. Arch Biochem Biophys 436 215-226... 

Alam P, Abdin MZ (2011) Over-expression of HMG-CoA reductase and amorpha-4, 11-diene synthase genes in Artemisia annua L. and its influence on artemisinin content. Plant Cell Rep 30 1919-1928... 

Bouwmeester, H.J., WaUaart, T.E., lanssen, M.H.A. et al (1999) Amorpha-4,11-diene synthase catalyses the first probable step in artemisinin biosynthesis. Phytochemistry, 52, 843 54. 

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