中药活性成分合成生物学研究进展

Research progress in synthetic biology of active compounds in Chinese medicinal plants

药用植物中存在许多具有显著药理活性的天然化合物,其结构复杂多样,为创新药物的研制提供了重要的分子结构。目前中药活性成分主要是通过种植植物获取,随着需求量日益增加,人们面临着野生资源遭到破坏、种植植物资源短缺等问题。由于大部分天然活性成分在生药中含量较低、结构复杂、难以化学合成,极大限制了药物的研发和使用,利用合成生物学的方法在微生物中异源生产天然化合物来解决资源问题成为当下研究的热点。中药活性成分合成生物学是从药用植物中发掘天然活性成分生物合成途径关键酶,并研究酶的功能和催化机制,然后利用酶元件在微生物中重构和优化,实现活性成分在微生物中的适配高效生产。该文介绍了合成生物学的发展过程,萜类、生物碱类、黄酮类的上游生物合成途径,系统综述代谢途径重构优化、发酵过程调控、菌株改造等合成生物学的相关策略,以及利用合成生物学异源生产中药活性成分的最新研究进展。该文为利用合成生物学方法,开发萜类、生物碱类、黄酮类等中药活性成分生产模式,从源头高效获取中药活性成分研究提供参考。

Mecicinal plants boast abundant natural compounds with significant pharmacological activity,and such compounds,featuring diversified and complex structures,can be used for research and development of drugs.At present,these natural compounds are directly extracted from herbs which,however,suffer from damaged wild resources and shortage of planting resources attributing to the increasing demand.Moreover,the low content in medicinal plants and complex structures are another challenge to the research and development of drugs.Heterologous synthesis with synthetic biology methods is a solution that has attracted wide attention.Synthetic biology for the production of natural active compounds in Chinese medicinal plants involves the exploration of key enzymes in compound biosynthetic pathways from plants,analysis of enzyme functions and mechanisms,and reconstruction and optimization of biosynthetic pathways in microorganisms for efficient synthesis of compounds.This study briefed the development process of synthetic biology and the biosynthetic pathways of terpenoids,alkaloids,and flavonoids,and summarized the related strategies of synthetic biology such as the reconstruction and optimization of metabolic pathways,regulation of fermentation process,and strain improvement,and the latest applications of heterogeneous synthetic biology in the production of natural compounds from Chinese medicinals.This study is expected to serve as a reference for the efficient production of terpenoids,alkaloids,flavonoids,and other active compounds from Chinese medicinal plants with strategies of synthetic biology.