Application of metabolic engineering to the production of scopolamine.
Scopolamine is an alkaloid widely used in medicine for its anticholinergic activity. The aim of this review is to show that metabolic engineering techniques constitute a suitable tool to improve the production of tropane alkaloids, focusing in particular on scopolamine. We present an overview of results obtained by various research groups, including our own, who have studied the overexpression of genes involved in the biosynthesis of scopolamine in different plant species that produce tropane alkaloids. Experiments carried out to improve production in hairy root cultures will also be described, as well as those attempting to biotransform hyoscyamine into scopolamine in roots and transgenic tobacco cells.
Palazón
Javier
J
Laboratori de Fisiologia Vegetal, Facultat de Farmacia, Universitat de Barcelona, Avda Diagonal 643, E-08028, Barcelona, Spain. javierpalazon@ub.edu
Navarro-Ocaña
Arturo
A
Hernandez-Vazquez
Liliana
L
Mirjalili
Mohammad Hossein
MH
D005818:Genetic Engineering / Q000379:methods*; D053858:Metabolic Networks and Pathways / Q000235:genetics; D030821:Plants, Genetically Modified / Q000378:metabolism*; D012601:Scopolamine / Q000096:biosynthesis*; D013678:Technology, Pharmaceutical
D012601:Scopolamine
Biotechnol Lett. 2006 Aug;28(16):1271-7
16802099
J Bacteriol. 1980 Mar;141(3):1134-41
6245060
Exp Cell Res. 1968 Apr;50(1):151-8
5650857
J Exp Bot. 2005 Feb;56(412):645-52
15642710
Phytochemistry. 2001 Jun;57(3):365-71
11393515
Plasmid. 1984 Sep;12(2):91-102
6095353
J Exp Bot. 2003 Sep;54(390):2065-70
12885861
Planta. 2007 Mar;225(4):887-96
17004056
Planta Med. 1999 Mar;65(2):144-8
10193206
Plant Cell Physiol. 2000 Jul;41(7):831-9
10965939
Curr Opin Plant Biol. 1998 Apr;1(2):173-8
10066577
Proc Natl Acad Sci U S A. 2004 Apr 27;101(17):6786-91
15084741
J Biol Chem. 1991 Mar 5;266(7):4648-53
1999440
Phytochemistry. 2000 Mar;53(6):623-37
10746874
J Exp Bot. 2005 Oct;56(420):2611-8
16105856
Plant Cell Physiol. 2000 Sep;41(9):1072-6
11100780
Biotechnol Prog. 2000 May-Jun;16(3):391-401
10835241
J Biotechnol. 2000 Aug 25;81(2-3):151-8
10989174
J Exp Bot. 2003 Jan;54(381):203-11
12493848
Plant Sci. 2001 Apr;160(5):1043-1053
11297802
Phytochemistry. 2002 Oct;61(3):323-9
12359518
Proc Natl Acad Sci U S A. 2006 Apr 4;103(14):5614-9
16565214
J Nat Prod. 2000 Sep;63(9):1249-52
11000029
Plant Cell Physiol. 1999 Mar;40(3):289-97
10353217
Proc Natl Acad Sci U S A. 2003 Jul 8;100(14):8595-600
12826618
Phytochemistry. 1994 Sep;37(2):391-400
7765621
Planta Med. 2002 Oct;68(10):859-68
12391546
Planta. 1990 Aug;182(1):136-41
24197009
Crit Rev Biotechnol. 2007 Jan-Mar;27(1):29-43
17364688
Trends Plant Sci. 2004 Sep;9(9):433-40
15337493
Plant Physiol. 1994 Jun;105(2):483-90
8066129
Phytochemistry. 2002 Apr;59(7):697-702
11909625
Plant Physiol. 1992 Oct;100(2):826-35
16653064
Proc Natl Acad Sci U S A. 1992 Dec 15;89(24):11799-803
1465402
Bioresour Technol. 2007 Jul;98(9):1748-53
16965915
J Plant Physiol. 2007 Apr;164(4):521-4
16904229
Planta. 1989 May;178(1):131-7
24212558
Proc Natl Acad Sci U S A. 1998 Apr 28;95(9):4876-81
9560196
Trends Biotechnol. 2005 Apr;23(4):180-5
15780709
Plant Physiol. 1993 Dec;103(4):1465-6
8290643
Proc Natl Acad Sci U S A. 1993 Oct 15;90(20):9591-5
8415746
Nat Biotechnol. 1996 Dec;14(13):1654-5
9634845
Plant Cell Physiol. 1999 Nov;40(11):1099-107
10635114
J Am Chem Soc. 1975 Nov 12;97(23):6826-30
1184883
Biotechnol Adv. 2002 May;20(2):101-53
14538059
Chem Biol. 2006 May;13(5):513-20
16720272
Proc Natl Acad Sci U S A. 2001 Jan 2;98(1):367-72
11134522
Nat Prod Rep. 2001 Oct;18(5):494-502
11699882
Nat Prod Rep. 2004 Apr;21(2):211-23
15042146
Planta. 1991 Oct;185(3):385-90
24186423
Plant Mol Biol. 1998 Dec;38(6):1101-11
9869416
Biotechnol Bioeng. 1998 Nov 5;60(3):375-84
10099442
Phytochemistry. 2006 Feb;67(4):327-37
16426652
Planta. 1989 May;178(1):123-30
24212557