School of Pharmacy, Henan University of Chinese Medicine, Zhengzhou 450046, China.
Co-Construction Collaborative Innovation Center for Chinese Medicine and Respiratory Diseases by Henan and Education Ministry of P. R. China, Henan University of Chinese Medicine, Zhengzhou 450046, China.
Molecules. 2022 Oct 14;27(20):6888. doi: 10.3390/molecules27206888.
Malaria is a life-threatening disease. Artemisinin-based combination therapy (ACT) is the preferred choice for malaria treatment recommended by the World Health Organization. At present, the main source of artemisinin is extracted from ; however, the artemisinin content in is only 0.1-1%, which cannot meet global demand. Meanwhile, the chemical synthesis of artemisinin has disadvantages such as complicated steps, high cost and low yield. Therefore, the application of the synthetic biology approach to produce artemisinin in vivo has magnificent prospects. In this review, the biosynthesis pathway of artemisinin was summarized. Then we discussed the advances in the heterologous biosynthesis of artemisinin using microorganisms ( and ) as chassis cells. With yeast as the cell factory, the production of artemisinin was transferred from plant to yeast. Through the optimization of the fermentation process, the yield of artemisinic acid reached 25 g/L, thereby producing the semi-synthesis of artemisinin. Moreover, we reviewed the genetic engineering in to improve the artemisinin content, which included overexpressing artemisinin biosynthesis pathway genes, blocking key genes in competitive pathways, and regulating the expression of transcription factors related to artemisinin biosynthesis. Finally, the research progress of artemisinin production in other plants (, , etc.) was discussed. The current advances in artemisinin biosynthesis may help lay the foundation for the remarkable up-regulation of artemisinin production in through gene editing or molecular design breeding in the future.
疟疾是一种危及生命的疾病。青蒿素类复方疗法（ACT）是世界卫生组织推荐的疟疾治疗首选方案。目前，青蒿素的主要来源是从 中提取的；然而， 中的青蒿素含量仅为 0.1-1%，无法满足全球需求。同时，青蒿素的化学合成存在步骤复杂、成本高、产率低等缺点。因此，应用合成生物学方法在体内生产青蒿素具有广阔的前景。本文综述了青蒿素的生物合成途径。然后我们讨论了利用微生物（ 和 ）作为底盘细胞异源生物合成青蒿素的进展。以酵母作为细胞工厂，将青蒿素的生产从植物转移到酵母中。通过优化发酵工艺，青蒿酸的产量达到 25 g/L，从而实现了青蒿素的半合成。此外，我们还综述了在 中进行遗传工程以提高青蒿素含量的研究进展，包括过表达青蒿素生物合成途径基因、阻断竞争途径中的关键基因以及调节与青蒿素生物合成相关的转录因子的表达。最后，讨论了其他植物（ 、 等）中青蒿素生产的研究进展。目前青蒿素生物合成的进展可能有助于为未来通过基因编辑或分子设计育种在 中显著上调青蒿素生产奠定基础。
