Whole-cell biotransformation of parthenolide by fungal strains

Biotransformation is increasingly recognized as a green, cost-effective and efficient strategy for generating chemodiversity. Previous work in our laboratory demonstrated that fungal secretomes—enzyme mixtures secreted by fungi can efficiently convert simple starting materials into complex molecules [ 1 ] [ 2 ] [ 3 ]. However, this approach is limited by the loss of intracellular enzymes and reduced activity of enzymes that rely on cofactors. To overcome these challenges, we developed a high-throughput whole-cell microbiotransformation platform based on fungal cultures grown in 96-well plates [ 4 ]. This method enables rapid screening of biotransformation capabilities across multiple fungal strains while minimizing substrate consumption. The platform leverages recent advances in UHPLC-HRMS/MS to facilitate compound identification and gain structural insight. This methodology was applied to the biotransformation of parthenolide, a sesquiterpene lactone from Tanacetum parthenium, known for its potent anti-inflammatory and anti-cancer properties [ 5 ]. Two strains of Botrytis and one of Sclerotinia from the Agroscope mycotheca were selected for their ability to generate uncommon structural features. Biotransformations were scaled up to liter-scale cultures, with parthenolide administered in incremental doses to enhance yield and reduce potential substrate inhibition. Reaction monitoring was conducted via UHPLC-DAD-CAD-MS. Purification of the products was achieved using high-resolution semi-preparative HPLC, combining geometric transfer and dry load injection. Structural elucidation was performed through comprehensive NMR and HRMS analyses. Using this workflow, we successfully synthesized a series of parthenolide derivatives, currently under evaluation as Wnt pathways inhibitors in triple-negative breast cancer cells. This sustainable approach provides a promising avenue for generating novel chemical scaffolds with potential bioactivities. Publication History Article published online: 05 March 2026 © 2026. Thieme. All rights reserved. Georg Thieme Verlag KG Oswald-Hesse-Straße 50, 70469 Stuttgart, Germany