Abstract
The terpenoid indole alkaloid (TIA) pathway in Catharanthus roseus produces two important anticancer drugs, vinblastine and vincristine, in very low yields. This study focuses on overexpressing several key genes in the upper part of the TIA pathway in order to increase flux toward downstream metabolites within hairy root cultures. Specifically, we constructed hairy root lines with inducible overexpression of 1-deoxy- D-xylulose synthase (DXS) or geraniol-10-hydroxylase (G10H). We also constructed hairy root lines with inducible expression of DXS and anthranilate synthase α subunit (ASA) or DXS and G10H. DXS overexpression resulted in a significant increase in ajmalicine by 67%, serpentine by 26% and lochnericine by 49% and a significant decrease in tabersonine by 66% and hörhammericine by 54%. Co-overexpression of DXS and G10H caused a significant increase in ajmalicine by 16%, lochnericine by 31% and tabersonine by 13%. Likewise, DXS and ASA overexpression displayed a significant increase in hörhammericine by 30%, lochnericine by 27% and tabersonine by 34%. These results point to the need for overexpressing multiple genes within the pathway to increase the flux toward vinblastine and vincristine.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 234-240 |
| Number of pages | 7 |
| Journal | Metabolic Engineering |
| Volume | 13 |
| Issue number | 2 |
| DOIs | |
| State | Published - Mar 1 2011 |
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Keywords
- Madagascar periwinkle
- Methyl-erythritol phosphate pathway
- Plant metabolic engineering
- Terpenoid indole alkaloid
- Tissue culture
Cite this
The expression of 1-deoxy-d-xylulose synthase and geraniol-10-hydroxylase or anthranilate synthase increases terpenoid indole alkaloid accumulation in Catharanthus roseus hairy roots. / Peebles, Christie A.M.; Sander, Guy W; Hughes, Erik H.; Peacock, Ryan; Shanks, Jacqueline V.; San, Ka Yiu.
In: Metabolic Engineering, Vol. 13, No. 2, 01.03.2011, p. 234-240.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - The expression of 1-deoxy-d-xylulose synthase and geraniol-10-hydroxylase or anthranilate synthase increases terpenoid indole alkaloid accumulation in Catharanthus roseus hairy roots
AU - Peebles, Christie A.M.
AU - Sander, Guy W
AU - Hughes, Erik H.
AU - Peacock, Ryan
AU - Shanks, Jacqueline V.
AU - San, Ka Yiu
PY - 2011/3/1
Y1 - 2011/3/1
N2 - The terpenoid indole alkaloid (TIA) pathway in Catharanthus roseus produces two important anticancer drugs, vinblastine and vincristine, in very low yields. This study focuses on overexpressing several key genes in the upper part of the TIA pathway in order to increase flux toward downstream metabolites within hairy root cultures. Specifically, we constructed hairy root lines with inducible overexpression of 1-deoxy- D-xylulose synthase (DXS) or geraniol-10-hydroxylase (G10H). We also constructed hairy root lines with inducible expression of DXS and anthranilate synthase α subunit (ASA) or DXS and G10H. DXS overexpression resulted in a significant increase in ajmalicine by 67%, serpentine by 26% and lochnericine by 49% and a significant decrease in tabersonine by 66% and hörhammericine by 54%. Co-overexpression of DXS and G10H caused a significant increase in ajmalicine by 16%, lochnericine by 31% and tabersonine by 13%. Likewise, DXS and ASA overexpression displayed a significant increase in hörhammericine by 30%, lochnericine by 27% and tabersonine by 34%. These results point to the need for overexpressing multiple genes within the pathway to increase the flux toward vinblastine and vincristine.
AB - The terpenoid indole alkaloid (TIA) pathway in Catharanthus roseus produces two important anticancer drugs, vinblastine and vincristine, in very low yields. This study focuses on overexpressing several key genes in the upper part of the TIA pathway in order to increase flux toward downstream metabolites within hairy root cultures. Specifically, we constructed hairy root lines with inducible overexpression of 1-deoxy- D-xylulose synthase (DXS) or geraniol-10-hydroxylase (G10H). We also constructed hairy root lines with inducible expression of DXS and anthranilate synthase α subunit (ASA) or DXS and G10H. DXS overexpression resulted in a significant increase in ajmalicine by 67%, serpentine by 26% and lochnericine by 49% and a significant decrease in tabersonine by 66% and hörhammericine by 54%. Co-overexpression of DXS and G10H caused a significant increase in ajmalicine by 16%, lochnericine by 31% and tabersonine by 13%. Likewise, DXS and ASA overexpression displayed a significant increase in hörhammericine by 30%, lochnericine by 27% and tabersonine by 34%. These results point to the need for overexpressing multiple genes within the pathway to increase the flux toward vinblastine and vincristine.
KW - Madagascar periwinkle
KW - Methyl-erythritol phosphate pathway
KW - Plant metabolic engineering
KW - Terpenoid indole alkaloid
KW - Tissue culture
UR - http://www.scopus.com/inward/record.url?scp=79952103915&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=79952103915&partnerID=8YFLogxK
U2 - 10.1016/j.ymben.2010.11.005
DO - 10.1016/j.ymben.2010.11.005
M3 - Article
VL - 13
SP - 234
EP - 240
JO - Metabolic Engineering
JF - Metabolic Engineering
SN - 1096-7176
IS - 2
ER -