Safeguarding artemisinin: integrating bioproduction innovation and resistance management for malaria eradication

Malaria persists as a global health emergency, with Plasmodium falciparum resistance to artemisinin (ART) critically undermining elimination campaigns. This review consolidates dual challenges of ART production and resistance, presenting a unified analysis of countermeasures. The examination encompasses biotechnological advances in ART biosynthesis, including metabolic engineering strategies applied in both native and heterologous hosts, alongside an assessment of approaches to mitigate agricultural constraints in Artemisia annua cultivation. Concurrently, the analysis focuses on the molecular mechanisms underpinning ART resistance, with particular emphasis on pfk13 mutations and their implications for therapeutic efficacy. Current treatments, notably artemisinin-based combination therapy (ACT), and novel strategies like triple and quadruple ACTs (TACTs/QACTs) are critically evaluated, emphasizing advantages, drawbacks, and geographical suitability. By bridging production and resistance paradigms, this review outlines a sustainable malaria control roadmap, advocating interdisciplinary collaboration to ensure ART's enduring efficacy.