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 Artemisia annua; however, the artemisinin content in A. annua 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 (Escherichia coli and Saccharomyces cerevisiae) 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 A. annua 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 (Nicotiana, Physcomitrella, etc.) was discussed. The current advances in artemisinin biosynthesis may help lay the foundation for the remarkable up-regulation of artemisinin production in A. annua through gene editing or molecular design breeding in the future.

Icariside I, a bioactive flavonoid derivative derived from Herba epimedii, demonstrates better pharmacological properties compared to its precursor icariin. Enzymatic conversion of icariin to icariside I using α-L-rhamnosidase represents an efficient biotechnological approach. In this study, we characterized a GH78 family α-L-rhamnosidase from Dictyoglomus thermophilum (DthRha) with promising biocatalytic properties. The recombinant DthRha displayed optimal activity at 55 °C and pH 6.0, with remarkable thermostability (retaining > 80% activity after 1 h at 45–65 °C) and pH stability (pH 5.0–7.0). The kinetic parameters K_m, k_cat and k_cat/K_m values for pNPR of 0.44 mM, 7.99 s⁻¹ and 18.16 s⁻¹ mM⁻¹, respectively. Notably, DthRha exhibited good organic solvent tolerance, retaining > 50% activity after 4 h in 10% DMSO. Applied in a DMSO cosolvent system, DthRha achieved 92.3% conversion of icariin to icariside I within 4 h under optimized conditions. Interestingly, elevating the substrate concentration to 10 mM resulted in a consistently high icariin conversion of 95.8%. The enzymatic hydrolysis method can be applied to the industrial production of Icariside I. Furthermore, DthRha not only cleaves the α-1,2 glycosidic bond between glucoside and rhamnoside in compounds like naringin, but also exhibits tolerance to organic solvents, making it suitable for the hydrolysis of other poorly soluble flavonoids.

Icariside I is a pharmacologically important prenylated flavonoid glycoside, yet its efficient biocatalytic production from icariin is hindered by the limited stability and recyclability of the enzymes involved. In this study, an α-L-rhamnosidase mutant R783A (Rha R783A) was heterologously expressed, purified, and immobilized within a Cu-based metal–organic framework (MOF) via a one-pot co-precipitation strategy. The resulting Rha R783A@MOF biocomposite exhibited enhanced stability compared to the free enzyme, retaining >90% residual activity after incubation at 60 °C for 2 h and 86.4% after 30 days of storage. It also demonstrated broad pH adaptability. In the biotransformation of icariin, Rha R783A@MOF achieved a 99.8% conversion rate and a 97.8% yield of icariside I. Furthermore, the biocomposite maintained an 88.9% yield after eight consecutive reuse cycles under high-temperature conditions (60 °C), demonstrating excellent operational stability. This work presents a robust and sustainable strategy for icariside I production, highlighting the potential of MOF microparticles as an effective platform for the biocatalytic synthesis of high-value flavonoid compounds.