Center of Plant Systems Biology and Biotechnology, Plovdiv, Bulgaria.
Group of Plant Cell Biotechnology and Metabolomics, The Stephan Angeloff Institute of Microbiology, Bulgarian Academy of Sciences, Plovdiv, Bulgaria.
Crit Rev Biotechnol. 2020 Jun;40(4):443-458. doi: 10.1080/07388551.2020.1731414. Epub 2020 Mar 16.
For centuries plants have been intensively utilized as reliable sources of food, flavoring, agrochemical and pharmaceutical ingredients. However, plant natural habitats are being rapidly lost due to climate change and agriculture. Plant biotechnology offers a sustainable method for the bioproduction of plant secondary metabolites using plant systems. The unique structural features of plant-derived secondary metabolites, such as their safety profile, multi-target spectrum and "metabolite likeness," have led to the establishment of many plant-derived drugs, comprising approximately a quarter of all drugs approved by the Food and Drug Administration and/or European Medicinal Agency. However, there are still many challenges to overcome to enhance the production of these metabolites from plant systems and establish a sustainable large-scale biotechnological process. These challenges are due to the peculiarities of plant cell metabolism, the complexity of plant secondary metabolite pathways, and the correct selection of bioreactor systems and bioprocess optimization. In this review, we present an integrated overview of the possible avenues for enhancing the biosynthesis of high-value marketable molecules produced by plant systems. These include metabolic engineering and CRISPR/Cas9 technology for the regulation of plant metabolism through overexpression/repression of single or multiple structural genes or transcriptional factors. The use of NMR-based metabolomics for monitoring metabolite concentrations and additionally as a tool to study the dynamics of plant cell metabolism and nutritional management is discussed here. Different types of bioreactor systems, their modification and optimal process parameters for the lab- or industrial-scale production of plant secondary metabolites are specified.
几个世纪以来，植物一直被广泛用作食物、调味料、农用化学品和药物成分的可靠来源。然而，由于气候变化和农业的原因，植物的自然栖息地正在迅速消失。植物生物技术为使用植物系统生物生产植物次生代谢物提供了一种可持续的方法。植物来源的次生代谢物具有独特的结构特征，例如安全性、多靶点谱和“代谢物相似性”，这使得许多植物来源的药物得以建立，这些药物约占美国食品和药物管理局和/或欧洲药品管理局批准的所有药物的四分之一。然而，仍然存在许多挑战需要克服，以提高这些代谢物在植物系统中的产量，并建立可持续的大规模生物技术工艺。这些挑战是由于植物细胞代谢的特殊性、植物次生代谢途径的复杂性以及生物反应器系统的正确选择和生物过程优化。在这篇综述中，我们对增强植物系统产生高价值商品分子的生物合成提出了综合的看法。这些方法包括代谢工程和 CRISPR/Cas9 技术，通过过表达/抑制单个或多个结构基因或转录因子来调节植物代谢。本文讨论了基于 NMR 的代谢组学在监测代谢物浓度方面的应用，以及作为研究植物细胞代谢动力学和营养管理的工具。此外，还讨论了不同类型的生物反应器系统及其改进，以及用于实验室或工业规模生产植物次生代谢物的最佳过程参数。
