A team led by Professor Zhang Fan from the School of Pharmaceutical Sciences at Wuhan University has published its latest study in Angewandte Chemie International Edition.

The paper, Unveiling Aziridine-Containing Natural Products by Genomic and Spectroscopic Approaches, presents a new method for discovering a new class of aziridine-containing macrolide natural products.

Aziridines, characterized by their high-strain three-membered nitrogen heterocyclic structure, are highly valuable in medicinal and synthetic chemistry. However, they are rare in nature, accounting for less than 0.6 percent of known compounds, with few new structures reported in the past seven years.

Using the unique nuclear magnetic resonance (NMR) signals of aziridines, the team identified gene clusters with potential aziridine biosynthetic capabilities in actinomycetes and isolated four novel natural products, desertolides A–D.

These compounds are the first to introduce a rare terminal 2-methylaziridine-2-carboxylate structural unit into a natural macrolide framework, expanding the structural diversity of natural aziridine compounds.

The biosynthesis of the aziridine unit involves a novel enzymatic reaction mechanism, contrary to the previously hypothesized oxidative cyclization process.

The study also identified a key enzyme, DesN, responsible for transferring the aziridine unit to the polyketide backbone, providing crucial evidence for understanding the incorporation of isolated aziridine pharmacophores.

Based on these findings, the team conducted large-scale genomic mining and identified 59 biosynthetic gene clusters with potential aziridine synthesis capabilities, spanning various natural product assembly systems.