ArticleACS central science2024
High-Throughput Identification of Crystalline Natural Products from Crude Extracts Enabled by Microarray Technology and microED.
Article in ACS central science, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed.
- Accelerating natural product discovery, characterization and engineering by biofoundries.Natural product reports · 2026Review
- Application of electron diffraction to rapid structural elucidation of crude reaction products.Communications chemistry · 2026Article
- Rapid Structural Analysis of Natural Products Using MicroED.Small (Weinheim an der Bergstrasse, Germany) · 2026Article
- Quantification of enantiomorphs in chiral crystalline powders through three-dimensional electron diffraction.Nature chemistry · 2025Article
- Discovery of NaJournal of natural products · 2025Article
- Structural Elucidation of Nucleophilic Compounds through Synergistic Coordination and Hydrogen Bonding in a Metal-Organic Framework.Journal of the American Chemical Society · 2025Article
- Combining MicroED and native mass spectrometry for structural discovery of enzyme-small molecule complexes.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Microcrystal Electron Diffraction-Guided Discovery of Fungal Metabolites.Journal of the American Chemical Society · 2025Article
- Microbial secondary metabolites: advancements to accelerate discovery towards application.Nature reviews. Microbiology · 2025Review
- Single-crystal structure of the spicy capsaicin.Acta crystallographica. Section C, Structural chemistry · 2025Article
- A comparison of microcrystal electron diffraction and X-ray powder diffraction for the structural analysis of metal-organic frameworks.Journal of applied crystallography · 2025Article
- Fast event-based electron counting for small-molecule structure determination by MicroED.Acta crystallographica. Section C, Structural chemistry · 2025Article
- Unraveling atomic complexity from frozen samples.Structural dynamics (Melville, N.Y.) · 2025Article
- Combining MicroED and native mass spectrometry for structural discovery of enzyme-biosynthetic inhibitor complexes.bioRxiv : the preprint server for biology · 2025Article
- Discovery of a Chimeric Polyketide Family as Cancer Immunogenic Chemotherapeutic Leads.Journal of the American Chemical Society · 2025Article
- Applying 3D ED/MicroED workflows toward the next frontiers.Acta crystallographica. Section C, Structural chemistry · 2024Article
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Authors and funding
19 authors.
Funding
Abstract
The structural determination of natural products (NPs) can be arduous because of sample heterogeneity. This often demands iterative purification processes and characterization of complex molecules that may be available only in miniscule quantities. Microcrystal electron diffraction (microED) has recently shown promise as a method to solve crystal structures of NPs from nanogram quantities of analyte. However, its implementation in NP discovery remains hampered by sample throughput and purity requirements, akin to traditional NP-discovery workflows. In the methods described herein, we leverage the resolving power of transmission electron microscopy (TEM) and the miniaturization capabilities of deoxyribonucleic acid (DNA) microarray technology to address these challenges through the establishment of an NP screening platform, array electron diffraction (ArrayED). In this workflow, an array of high-performance liquid chromatography (HPLC) fractions taken from crude extracts was deposited onto TEM grids in picoliter-sized droplets. This multiplexing of analytes on TEM grids enables 1200 or more unique samples to be simultaneously inserted into a TEM instrument equipped with an autoloader. Selected area electron diffraction analysis of these microarrayed grids allows for the rapid identification of crystalline metabolites. In this study, ArrayED enabled structural characterization of 14 natural products, including four novel crystal structures and two novel polymorphs, from 20 crude extracts. Moreover, we identify several chemical species that would not be detected by standard mass spectrometry (MS) or ultraviolet-visible (UV/vis) spectroscopy and crystal forms that would not be characterized using traditional methods.
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