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
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
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DOI：
10.1016/j.ymben.2010.11.005
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发表时间：
2011-03-01
影响因子：
8.4
通讯作者：
San, Ka-Yiu
中科院分区：
文献类型：
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作者：
Peebles, Christie A. M.;Sander, Guy W.;San, Ka-Yiu
长春花中的萜类吲哚生物碱(TIA)途径以很低的产率产生两种重要的抗癌药物长春花碱和长春新碱。这项研究集中在TIA途径上部的几个关键基因的过度表达，以增加毛状根培养中向下游代谢产物的通量。具体地说，我们构建了可诱导高表达1-脱氧-D-木糖合成酶(DXS)或香叶醇-10-羟基酶(G10H)的毛状根系。我们还构建了诱导表达DXS和邻氨基苯甲酸合成酶α亚基(ASA)或DXS和G10H的毛状根系。DXS的过表达导致阿玛利辛、蛇纹碱和洛尼西林的含量分别显著增加67%、26%和49%，而他伯松碱和霍汉美辛的含量显著减少66%和54%。DXS和G10H的共过表达显著增加了阿玛利辛16%、洛克尼西林31%和丹参碱13%。同样，DXS和ASA过表达显著增加了30%的霍尔海默碱、27%的洛可尼辛和34%的丹参碱。这些结果表明，需要在该途径中过度表达多个基因，以增加长春花碱和长春新碱的流量。(C)2010 Elsevier Inc.保留所有权利。
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 alpha 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 horhammericine 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 increasein horhammericine 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. (C) 2010 Elsevier Inc. All rights reserved.