The seco-iridoid pathway from Catharanthus roseus

被引:374
作者
Miettinen, Karel [1 ]
Dong, Lemeng [2 ]
Navrot, Nicolas [3 ]
Schneider, Thomas [4 ]
Burlat, Vincent [5 ,6 ,7 ,8 ]
Pollier, Jacob [9 ,10 ]
Woittiez, Lotte [4 ]
van der Krol, Sander [2 ]
Lugan, Raphael [3 ]
Ilc, Tina
Verpoorte, Robert [1 ]
Oksman-Caldentey, Kirsi-Marja [11 ]
Martinoia, Enrico [4 ]
Bouwmeester, Harro [2 ]
Goossens, Alain [9 ,10 ]
Memelink, Johan [1 ]
Werck-Reichhart, Daniele [3 ]
机构
[1] Leiden Univ, Inst Biol Leiden, Sylvius Lab, NL-2300 RA Leiden, Netherlands
[2] Wageningen Univ, Lab Plant Physiol, NL-6708 PB Wageningen, Netherlands
[3] Univ Strasbourg, CNRS, Inst Biol Mol Plantes, Unite Propre Rech 2357, F-67000 Strasbourg, France
[4] Univ Zurich, Inst Plant Biol, CH-8008 Zurich, Switzerland
[5] CNRS, F-31326 Castanet Tolosan, France
[6] Univ Toulouse, UMR 5546, F-31326 Castanet Tolosan, France
[7] UPS, F-31326 Castanet Tolosan, France
[8] Lab Rech Sci Vegetales, UMR 5546, F-31326 Castanet Tolosan, France
[9] Univ Ghent VIB, Dept Plant Syst Biol, B-9052 Ghent, Belgium
[10] Univ Ghent, Dept Plant Biotechnol & Bioinformat, B-9052 Ghent, Belgium
[11] VTT Tech Res Ctr Finland, Ind Biotechnol, FI-02044 Espoo, Finland
基金
欧盟第七框架计划;
关键词
INDOLE ALKALOID BIOSYNTHESIS; SUBCELLULAR ORGANIZATION; RAUWOLFIA-SERPENTINA; STATISTICAL-MODEL; PLANTS; EXPRESSION; PROTEINS; SYNTHASE; ENZYME; CYTOCHROME-P450;
D O I
10.1038/ncomms4606
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
The (seco) iridoids and their derivatives, the monoterpenoid indole alkaloids (MIAs), form two large families of plant-derived bioactive compounds with a wide spectrum of high-value pharmacological and insect-repellent activities. Vinblastine and vincristine, MIAs used as anticancer drugs, are produced by Catharanthus roseus in extremely low levels, leading to high market prices and poor availability. Their biotechnological production is hampered by the fragmentary knowledge of their biosynthesis. Here we report the discovery of the last four missing steps of the (seco) iridoid biosynthesis pathway. Expression of the eight genes encoding this pathway, together with two genes boosting precursor formation and two downstream alkaloid biosynthesis genes, in an alternative plant host, allows the heterologous production of the complex MIA strictosidine. This confirms the functionality of all enzymes of the pathway and highlights their utility for synthetic biology programmes towards a sustainable biotechnological production of valuable (seco) iridoids and alkaloids with pharmaceutical and agricultural applications.
引用
收藏
页数:11
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