Ghent University, Department of Plant Biotechnology and Bioinformatics, 9052 Ghent, Belgium; VIB Center for Plant Systems Biology, 9052 Ghent, Belgium.
Ghent University, Department of Plant Biotechnology and Bioinformatics, 9052 Ghent, Belgium; VIB Center for Plant Systems Biology, 9052 Ghent, Belgium.
Metab Eng. 2018 Jul;48:150-162. doi: 10.1016/j.ymben.2018.05.016. Epub 2018 May 28.
To fend off microbial pathogens and herbivores, plants have evolved a wide range of defense strategies such as physical barriers, or the production of anti-digestive proteins or bioactive specialized metabolites. Accumulation of the latter compounds is often regulated by transcriptional activation of the biosynthesis pathway genes by the phytohormone jasmonate-isoleucine. Here, we used our recently developed flower petal transformation method in the medicinal plant Catharanthus roseus to shed light on the complex regulatory mechanisms steering the jasmonate-modulated biosynthesis of monoterpenoid indole alkaloids (MIAs), to which the anti-cancer compounds vinblastine and vincristine belong. By combinatorial overexpression of the transcriptional activators BIS1, ORCA3 and MYC2a, we provide an unprecedented insight into the modular transcriptional control of MIA biosynthesis. Furthermore, we show that the expression of an engineered de-repressed MYC2a triggers a tremendous reprogramming of the MIA pathway, finally leading to massively increased accumulation of at least 23 MIAs. The current study unveils an innovative approach for future metabolic engineering efforts for the production of valuable bioactive plant compounds in non-model plants.
为了抵御微生物病原体和草食动物，植物进化出了多种防御策略，如物理屏障，或产生抗消化蛋白或生物活性特殊代谢物。这些化合物的积累通常受到植物激素茉莉酸异亮氨酸对生物合成途径基因转录激活的调节。在这里，我们使用最近在药用植物长春花中开发的花瓣转化方法，阐明了调控茉莉酸调节的单萜吲哚生物碱（MIAs）生物合成的复杂调控机制，其中包括抗癌化合物长春碱和长春新碱。通过组合过表达转录激活因子 BIS1、ORCA3 和 MYC2a，我们对 MIA 生物合成的模块化转录控制提供了前所未有的见解。此外，我们表明，工程化去阻遏 MYC2a 的表达引发了 MIA 途径的巨大重编程，最终导致至少 23 种 MIAs 的大量积累。本研究揭示了一种创新方法，可用于未来在非模式植物中生产有价值的生物活性植物化合物的代谢工程。
