Whole-cell fungal biotransformation as a tool for structural characterisation of relevant human CYP450 mediated metabolites: the case of solanidine

The cytochrome P450 enzyme superfamily is responsible for the phase 1 metabolisation of approximately 70% of all clinically prescribed drugs [ 1 ]. Due to the highly polymorphic nature of major CYP450 isoforms – particularly CYP2D6 – there is considerable intra- and inter-individual variability in metabolic activity. Identifying specific metabolic biomarkers is therefore crucial for understanding differential drug responses and for advancing personalised medicine. In our previous studies, we showed the potential of solanidine, a steroidal alkaloid found in potatoes, and its CYP2D6-mediated metabolites as dietary biomarkers for CYP2D6 activity in a clinical setting [ 2 ]. Structural characterisation of these metabolites remains challenging due to low metabolisation yields by human CYP450s. To overcome this, we employ whole-cell fungal biotransformation to produce larger quantities of its metabolites. In this study, we combine CYP-mediated biotransformation with untargeted metabolomics to investigate the phase I metabolism of solanidine. Solanidine was subjected to phase I metabolisation using human liver microsomes (HLMs), and the resulting metabolite profile was analysed using high-resolution mass spectrometry, revealing 5 solanidine derived metabolites. Subsequently, whole-cell fungal biotransformation using Botrytis cinerea was employed as a complementary model system, revealing solanidine-derived metabolites common to both the HLM and whole-cell fungal systems [ 3 ]. This demonstrates the potential of whole-cell fungi to mimic human CYP450 metabolism and highlight the utility of whole-cell fungal biotransformations as a powerful tool for producing metabolites of interest in higher yields. This provides a scalable platform for metabolite generation and isolation, enabling comprehensive structural characterisation of metabolites produced by human CYP450 enzymes. Publication History Article published online: 05 March 2026 © 2026. Thieme. All rights reserved. Georg Thieme Verlag KG Oswald-Hesse-Straße 50, 70469 Stuttgart, Germany