Abietane diterpenoids (e.g. aethiopinone, 1-oxoaethiopinone, salvipisone, and ferruginol), synthesized in the roots of different Salvia species, have a great medicinal value for a variety of known biological activities. In particular, aethiopinone has a promising citotoxic activity against different human tumor cell lines [1,2]. The accumulation at low levels and the limited possibility to synthesize chemically these products, prompted us to optimize their production by targeting genes of the MEP-derived pathway, from which they derive. -Deoxy-D- Xylulose-5-Phosphate Synthase ( -Deoxy-D-Xylulose-5- Phosphate Reductoisomerase Driving metabolic flux towards high content of abietane-type diterpenes in Salvia sclarea hairy roots  Elicitation studies with methyl-jasmonate and coronatine have indicated that the induced-expression of genes acting up-stream [1 DXS) and 1 (DXR)] or more downstream level of abietane-type diterpenes in S. sclarea hairy roots. Here, we GGPPS) and CPPS)] of this pathway correlates with high- report our current efforts to direct the metabolic flux towards this interesting class of compounds in Salvia sclarea hairy roots by tuning the expression of genes controlling putative rate-limiting steps (DXS, DXR, GGPPS, CPPS, alone or in combination), silencing of a gene acting at a lateral competitive route [ (Ent-CPPS)] or by over-expression of transcription factors that regulate coordinately several genes of the pathway (WRKY and MYC2). Overall, these complementary approaches successfully enhanced the content of this class of compounds in engineered hairy roots (from 2- up to 8-fold higher than the content in the control line), paving the way to a rational design of a production platform to yield reliable amounts for a deeper understanding of their molecular targets [geranylgeranyl-diphosphate diphosphate synthase ( synthase ( copalyl- Ent-copalyl-diphosphate synthase and potential future commercialization.

High-level of bioactive abietane diterpenes in S. sclarea hairy roots by overexpression of SsGGPPS and/or SsCPPS genes.

Alfieri M
Investigation
;
Vaccaro MC
Investigation
;
Fasano R
Writing – Original Draft Preparation
;
Malafronte N
Investigation
;
De Tommasi N
Investigation
;
2015

Abstract

Abietane diterpenoids (e.g. aethiopinone, 1-oxoaethiopinone, salvipisone, and ferruginol), synthesized in the roots of different Salvia species, have a great medicinal value for a variety of known biological activities. In particular, aethiopinone has a promising citotoxic activity against different human tumor cell lines [1,2]. The accumulation at low levels and the limited possibility to synthesize chemically these products, prompted us to optimize their production by targeting genes of the MEP-derived pathway, from which they derive. -Deoxy-D- Xylulose-5-Phosphate Synthase ( -Deoxy-D-Xylulose-5- Phosphate Reductoisomerase Driving metabolic flux towards high content of abietane-type diterpenes in Salvia sclarea hairy roots  Elicitation studies with methyl-jasmonate and coronatine have indicated that the induced-expression of genes acting up-stream [1 DXS) and 1 (DXR)] or more downstream level of abietane-type diterpenes in S. sclarea hairy roots. Here, we GGPPS) and CPPS)] of this pathway correlates with high- report our current efforts to direct the metabolic flux towards this interesting class of compounds in Salvia sclarea hairy roots by tuning the expression of genes controlling putative rate-limiting steps (DXS, DXR, GGPPS, CPPS, alone or in combination), silencing of a gene acting at a lateral competitive route [ (Ent-CPPS)] or by over-expression of transcription factors that regulate coordinately several genes of the pathway (WRKY and MYC2). Overall, these complementary approaches successfully enhanced the content of this class of compounds in engineered hairy roots (from 2- up to 8-fold higher than the content in the control line), paving the way to a rational design of a production platform to yield reliable amounts for a deeper understanding of their molecular targets [geranylgeranyl-diphosphate diphosphate synthase ( synthase ( copalyl- Ent-copalyl-diphosphate synthase and potential future commercialization.
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/11386/4703389
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