Recent advances in the study of amorpha-4,11-diene synthase and its metabolic engineering
- Author:
- No author available
- Journal Title:
- ACTA PHARMACEUTICA SINICA
- Issue:
- 12
- DOI:
- 10.3321/j.issn:0513-4870.2009.12.002
- Key Word:
- 紫穗槐-4,11-二烯;紫穗槐-4,11-二烯合酶;青蒿素;工程菌;amorpha-4,11-diene;amorpha-4,11-diene synthasc;artemisinin;engineering microorganism
Abstract： Amorpha-4,11-diene synthase(ADS)can convert farnesyl pyrophosphate(FPP)to amorpha-4,11-diene,a precursor of artemisinin. ADS plays an important role in the biosynthesis of artemisinin.This review summarizes the molecular biology and metabolic engineering study of ADS in recent years.The genomic DNA and its cDNA sequences of amorpha-4.11-diene synthase were cloned from Artemisia annua L.The eDNA encoding amorpha-4.11-diene synthase contains a 1641 bp open reading frame coding for 546 amino acids.ADS shows a broad pH optimum and an absolute requirement for divalent metal ions as cofactors.The specificity of ADS to the substrates and products is not high and the formation of amorpha-4,11-diene by ADS from FPP is achieved by an initial 1,6-closure with subsequent 1,10-closure.The ADS cDNA cloned from Artemisia annua L,or totally synthesized by PCR,was introduced into different hosts including E .coli,S.cerevisiae,Nicotiana tabacum L.Arabidopsis thaliana and A.nidulans resulting in varied engineering microorganisms and cells producing amorpha-4,11-diene.The way to improve the production of amorpha4,11-diene was investigated by two strategies such as improving the supply of substrate and directing FPP flux to amorpha-4,11-diene production from competing pathways.
- [1]Zhen-Qiu Li,Yan Liu,Ben-Ye Liu,etc.Cloning, E. coli Expression and Molecular Analysis of Amorpha-4,11-Diene Synthase from a High-Yield Strain of Artemisia annua L.[J].2006,(12).
- [2]孔建强,程克棣,王丽娜,等.HMG-CoA还原酶和FPP合酶基因拷贝数对紫穗槐-4,11-二烯酵母工程菌产量的影响[J].2007,(12).
- [3]Picaud S,Olofsson L,Brodelius M,etc.Expression, purification, and characterization of recombinant amorpha-4, 11-diene synthase from Artemisia annua L.[J].2005,436(2).
- [4]Newman JD,Marshall J,Chang M,etc.High-level production of amorpha-4,11-diene in a two-phase partitioning bioreactor of metabolically engineered Escherichia coli[J].2006,95(4).
- [5]Keasling JD,Lubertozzi D.Expression of a synthetic Artemesia annua amorphadiene synthase in Aspergillus nidulans yields altered product distribution.[J].2008,35(10).
- [6]Kirby J,Chan R,Keasling JD,etc.Redirection of flux through the FPP branch-point in Saccharomyces cerevisiae by down-regulating squalene synthase[J].2008,100(2).
- [7]Woerdenbag HJ,Pras N,Quax WJ,etc.Isolation and identification of dihydroartemisinic acid from Artemisia annua and its possible role in the biosynthesis of artemisinin.[J].1999,62(3).
- [8]Pitera DJ,Paddon CJ,Newman JD,etc.Balancing a heterologous mevalonate pathway for improved isoprenoid production in Escherichia coli.[J].2007,9(2).
- [9]Lindahl AL,Olsson ME,Mercke P,etc.Production of the artemisinin precursor amorpha-4,11-diene by engineered Saccharomyces cerevisiae[J].2006,28(8).
- [10]Vincent J J, Martin,Douglas J, Pitera,Sydnor T, Withers,etc.Engineering a mevalonate pathway in Escherichia coli for production of terpenoids.[J].2003,21(7).
- [11]Anand Akhila,Raghunath S. Thakur,Satya P. Popli.Biosynthesis of artemisinin in Artemisia annua[J].1987,26(7).
- [12]M S, Nair,D V, Basile.Bioconversion of arteannuin B to artemisinin.[J].1993,56(9).
- [13]Rajender S. Sangwan,K. Agarwal,R. Luthra,etc.Biotransformation of arteannuic acid into arteannuin-B and artemisinin in Artemisia annua[J].1993,34(5).
- [14]Park SH.,Kim SU.,Chang YJ.,etc.Amorpha-4,11-diene synthase of Artemisia annua: cDNA isolation and bacterial expression of a terpene synthase involved in artemisinin biosynthesis[J].2000,383(2).
- [15]Mercke P.,Bouwmeester HJ.,Posthumus MA.,etc.Molecular cloning, expression, and characterization of amorpha-4,11-diene synthase, a key enzyme of artemisinin biosynthesis in Artemisia annua L.[J].2000,381(2).
- [16]Anthony JR,Anthony LC,Nowroozi F,etc.Optimization of the mevalonate-based isoprenoid biosynthetic pathway in Escherichia coli for production of the anti-malarial drug precursor amorpha-4,11-diene.[J].2009,11(1).
- [17]Chang MC,Ham TS,Withers ST,etc.Production of the antimalarial drug precursor artemisinic acid in engineered yeast.[J].2006,440(7086).
- [18]Chen T,Li M,Zhang R.Dihydroartemisinin induces apoptosis and sensitizes human ovarian cancer cells to carboplatin therapy.[J].2009,13(7).
- [19]Brodelius M,Mercke P,He XF,etc.Amorpha-4,11-diene synthase: Mechanism and stereochemistry of the enzymatic cyclization of farnesyl diphosphate[J].2006,448(1).
- [20]Quax WJ,Pras N,Eelco Wallaart-T.Seasonal variations of Artemisinin and its biosynthetic precursors in tetraploid Artemisia annua plants compared with the diploid wild-type.[J].1999,65(8).
- [21]T E, Wallaart,H J, Bouwmeester,J, Hille,etc.Amorpha-4,11-diene synthase: cloning and functional expression of a key enzyme in the biosynthetic pathway of the novel antimalarial drug artemisinin.[J].2001,212(3).
- [22]Bouwmeester HJ,Janssen MHA,Van Loo B,etc.Amorpha-4,11-diene synthase catalyses the first probable step in artemisinin biosynthesis[J].1999,52(5).
- [23]Chang YJ,Kim SH,Kim SU.Tissue specificity and developmental pattern of amorpha-4,11-diene synthase (ADS) proved by ADS promoter-driven GUS expression in the heterologous plant, Arabidopsis thaliana.[J].2008,74(2).
- [24]Farouk S. El-Feraly,Ibrahim A. Al-Meshal,Mohammed A. Al-Yahya,etc.On the possible role of qinghao acid in the biosynthesis of artemisinin[J].1986,25(12).
- [25]Sang-Ki Rhee,Keon Heo,Si-Hyung Park,etc.Cyclization Mechanism of Amorpha-4,11-diene Synthase, a Key Enzyme in Artemisinin Biosynthesis[J].2006,69(5).
- [26]Hale V,Diagana TT,Keasling JD,etc.Microbially derived artemisinin: a biotechnology solution to the global problem of access to affordable antimalarial drugs.[J].2007,77(6 Suppl.).
- [27]Jiang-Qiang K.,Wei W.,Li-Na W.,etc.The improvement of amorpha-4,11-diene production by a yeast-conform variant[J].2009,106(3).
- [28]Anand Akhila,Kumkum Rani,Raghunath S. Thakur.Biosynthesis of artemisinic acid in Artemisia annua[J].1990,29(7).