Amorpha-4,11-diene

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. 

Another type of decalin-containing sesquiterpene is seen in the structures of a-cadinene and amorpha-4,11-diene. a-Cadinene (Figure 5.33) is... 

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... 

Fig. 4 A Cyclization of FPP to amorpha-4,11-diene by AMDS as described by Kim et al. and Picaud et al. [ 10,11 ]. B Cyclization of FPP to helmonthogermabicradienyldiphosphate synthase carbocation...

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. 

Fig. 5 Computerized 3D structure of amorpha-4,11-diene. Residues marked with red belong to the conserved metal ion binding amino acid sequence IDxxDD. The 3D model of the amorphadiene synthase (AMDS) courtesy of Wolfgang Brandt, Leibniz Institute of Plant Biochemistry Halle, Germany...

K. et al. (2013) Statistical experimental design guided optimization of a one-pot biphasic multienzyme total synthesis of amorpha-4,11-diene. PLoS One, 8, e79650. 

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]... 

Komori A, Suzuki M, Seki H, Nishizawa T, Meyer JJM, Shimizu H, Yokoyama S, Muranaka T (2013) Comparative functional analysis of CYP71AV1 natural variants reveals an important residue for the successive oxidation of amorpha-4,11-diene. FEES Lett 587 278-284... 

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