Inspired by taxol: biosynthesis and engineering of hypericin and other phytochemicals in Hypericum

Insights from paclitaxel research inspire elucidation of hypericin biosynthesis, highlighting gene identification, multi-omics integration, and biotechnological strategies enabling scalable and sustainable production of valuable Hypericum secondary metabolites. Paclitaxel (Taxol^®), a major plant-derived anticancer drug, exemplifies how research on complex natural products can lead to both breakthrough therapies and innovative strategies for scalable production. Building on this model, this review examines how advances in paclitaxel research have inspired new approaches to studying and producing other pharmaceutically important metabolites, particularly hypericins in Hypericum species. Complementary strategies, ranging from in vitro cultures and elicitor treatments to metabolomic and transcriptomic profiling, have shown promise in enhancing hypericin production, paralleling advances achieved with paclitaxel. Despite their known antiviral and anticancer properties, the biosynthetic pathway of hypericins remains only partially resolved. Current evidence supports a polyketide origin involving emodin and related intermediates, yet key enzymatic steps, particularly those leading to dimeric structures, are still unknown. Although candidate enzymes such as the polyketide synthase HpPKS2 have been identified in Hypericum species, much of the pathway remains unresolved. Given the biosynthetic parallels, fungal systems synthesizing related polyketide metabolites represent promising comparative models for elucidating the hypericin pathway and advancing metabolic engineering efforts. Insights derived from paclitaxel research may thus guide future strategies for elucidating, optimizing, and sustainably producing hypericins and other specialized metabolites across the genus Hypericum.