title: Application of metabolic engineering to the production of scopolamine.
abstract: 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.
authors.affiliation: Laboratori de Fisiologia Vegetal, Facultat de Farmacia, Universitat de Barcelona, Avda Diagonal 643, E-08028, Barcelona, Spain. javierpalazon@ub.edu
authors.forename: Javier
authors.initials: J
authors.lastname: Palazón
authors.forename: Arturo
authors.initials: A
authors.lastname: Navarro-Ocaña
authors.forename: Liliana
authors.initials: L
authors.lastname: Hernandez-Vazquez
authors.forename: Mohammad Hossein
authors.initials: MH
authors.lastname: Mirjalili
mesh_terms: 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
chemical_list: D012601:Scopolamine
references.citation: Biotechnol Lett. 2006 Aug;28(16):1271-7
references.pmid: 16802099
references.citation: J Bacteriol. 1980 Mar;141(3):1134-41
references.pmid: 6245060
references.citation: Exp Cell Res. 1968 Apr;50(1):151-8
references.pmid: 5650857
references.citation: J Exp Bot. 2005 Feb;56(412):645-52
references.pmid: 15642710
references.citation: Phytochemistry. 2001 Jun;57(3):365-71
references.pmid: 11393515
references.citation: Plasmid. 1984 Sep;12(2):91-102
references.pmid: 6095353
references.citation: J Exp Bot. 2003 Sep;54(390):2065-70
references.pmid: 12885861
references.citation: Planta. 2007 Mar;225(4):887-96
references.pmid: 17004056
references.citation: Planta Med. 1999 Mar;65(2):144-8
references.pmid: 10193206
references.citation: Plant Cell Physiol. 2000 Jul;41(7):831-9
references.pmid: 10965939
references.citation: Curr Opin Plant Biol. 1998 Apr;1(2):173-8
references.pmid: 10066577
references.citation: Proc Natl Acad Sci U S A. 2004 Apr 27;101(17):6786-91
references.pmid: 15084741
references.citation: J Biol Chem. 1991 Mar 5;266(7):4648-53
references.pmid: 1999440
references.citation: Phytochemistry. 2000 Mar;53(6):623-37
references.pmid: 10746874
references.citation: J Exp Bot. 2005 Oct;56(420):2611-8
references.pmid: 16105856
references.citation: Plant Cell Physiol. 2000 Sep;41(9):1072-6
references.pmid: 11100780
references.citation: Biotechnol Prog. 2000 May-Jun;16(3):391-401
references.pmid: 10835241
references.citation: J Biotechnol. 2000 Aug 25;81(2-3):151-8
references.pmid: 10989174
references.citation: J Exp Bot. 2003 Jan;54(381):203-11
references.pmid: 12493848
references.citation: Plant Sci. 2001 Apr;160(5):1043-1053
references.pmid: 11297802
references.citation: Phytochemistry. 2002 Oct;61(3):323-9
references.pmid: 12359518
references.citation: Proc Natl Acad Sci U S A. 2006 Apr 4;103(14):5614-9
references.pmid: 16565214
references.citation: J Nat Prod. 2000 Sep;63(9):1249-52
references.pmid: 11000029
references.citation: Plant Cell Physiol. 1999 Mar;40(3):289-97
references.pmid: 10353217
references.citation: Proc Natl Acad Sci U S A. 2003 Jul 8;100(14):8595-600
references.pmid: 12826618
references.citation: Phytochemistry. 1994 Sep;37(2):391-400
references.pmid: 7765621
references.citation: Planta Med. 2002 Oct;68(10):859-68
references.pmid: 12391546
references.citation: Planta. 1990 Aug;182(1):136-41
references.pmid: 24197009
references.citation: Crit Rev Biotechnol. 2007 Jan-Mar;27(1):29-43
references.pmid: 17364688
references.citation: Trends Plant Sci. 2004 Sep;9(9):433-40
references.pmid: 15337493
references.citation: Plant Physiol. 1994 Jun;105(2):483-90
references.pmid: 8066129
references.citation: Phytochemistry. 2002 Apr;59(7):697-702
references.pmid: 11909625
references.citation: Plant Physiol. 1992 Oct;100(2):826-35
references.pmid: 16653064
references.citation: Proc Natl Acad Sci U S A. 1992 Dec 15;89(24):11799-803
references.pmid: 1465402
references.citation: Bioresour Technol. 2007 Jul;98(9):1748-53
references.pmid: 16965915
references.citation: J Plant Physiol. 2007 Apr;164(4):521-4
references.pmid: 16904229
references.citation: Planta. 1989 May;178(1):131-7
references.pmid: 24212558
references.citation: Proc Natl Acad Sci U S A. 1998 Apr 28;95(9):4876-81
references.pmid: 9560196
references.citation: Trends Biotechnol. 2005 Apr;23(4):180-5
references.pmid: 15780709
references.citation: Plant Physiol. 1993 Dec;103(4):1465-6
references.pmid: 8290643
references.citation: Proc Natl Acad Sci U S A. 1993 Oct 15;90(20):9591-5
references.pmid: 8415746
references.citation: Nat Biotechnol. 1996 Dec;14(13):1654-5
references.pmid: 9634845
references.citation: Plant Cell Physiol. 1999 Nov;40(11):1099-107
references.pmid: 10635114
references.citation: J Am Chem Soc. 1975 Nov 12;97(23):6826-30
references.pmid: 1184883
references.citation: Biotechnol Adv. 2002 May;20(2):101-53
references.pmid: 14538059
references.citation: Chem Biol. 2006 May;13(5):513-20
references.pmid: 16720272
references.citation: Proc Natl Acad Sci U S A. 2001 Jan 2;98(1):367-72
references.pmid: 11134522
references.citation: Nat Prod Rep. 2001 Oct;18(5):494-502
references.pmid: 11699882
references.citation: Nat Prod Rep. 2004 Apr;21(2):211-23
references.pmid: 15042146
references.citation: Planta. 1991 Oct;185(3):385-90
references.pmid: 24186423
references.citation: Plant Mol Biol. 1998 Dec;38(6):1101-11
references.pmid: 9869416
references.citation: Biotechnol Bioeng. 1998 Nov 5;60(3):375-84
references.pmid: 10099442
references.citation: Phytochemistry. 2006 Feb;67(4):327-37
references.pmid: 16426652
references.citation: Planta. 1989 May;178(1):123-30
references.pmid: 24212557