A Systematic Review of Alternative Artemisinin Production Strategies.

Artemisinin (ART) production faces bottlenecks due to low and variable yields from its natural source, Artemisia annua. This limitation, coupled with expanding therapeutic potential beyond malaria, highlights the need for innovative production solutions. This systematic review aims to synthesize the evidence on alternative production platforms for ART. We searched PubMed, Scopus, Web of Science, and Google Scholar for studies published primarily between 2020 and 2025. Some search terms included "Artemisinin", "Artemisia annua", "biosynthesis", "in vitro culture", and "artificial intelligence". We included primary research articles reporting on strategies for ART production. We narratively synthesized data by production theme. Our review of 30 studies identified four frontiers for ART production: (1) Enhancement in A. annua ART content; (2) In vitro platforms focusing on callus and cell suspension cultures, which offer precise control but face scale-up bottlenecks; (3) Heterologous expression in non-Artemisia plants; and (4) Scalable semi-synthetic routes using microbially fermented precursors and chemical conversion. Furthermore, the review highlights the emerging role of AI-driven predictive modeling in source discovery and process optimization. By integrating these innovations, a robust roadmap exists for sustainable ART production.