Fig. 2. Applications of advanced analytical technologies empowering modern natural product-based drug discovery.

a | An illustrative example of the application of liquid chromatography–high-resolution mass spectrometry (LC–HRMS) metabolomics in the screening of natural product (NP) extracts is the work of Kurita et al.⁵⁸, in which 234 bacterial extracts were subjected to image-based phenotypic bioactivity screening and LC–HRMS metabolomics. Clustering of the resulting data allowed prioritization of promising extracts for further analysis, resulting in the discovery of the new NPs, quinocinnolinomycins A–D. b | Another illustrative example of LC–HRMS screening of NP extracts is the work of Clevenger et al.⁸⁵, who obtained novel NP extracts through heterologous expression of fungal artificial chromosomes (FACs) containing uncharacterized biosynthetic gene clusters (BGCs) from diverse fungal species in Aspergillus nidulans. Analysis of the LC–HRMS metabolomics data with a FAC-Score algorithm directed the simultaneous discovery of 15 new NPs and the characterization of their BGCs.