Abstract

The flavin-dependent N-monooxygenase SidA from Aspergillus fumigatus catalyzes the conversion of l -ornithine to N5-hydroxy- l -ornithine. This product is incorporated into hydroxamate containing siderophores, which are iron chelators required for growth during A. fumigatus infection in mammals. The activity of SidA has been shown to be required for siderophore biosynthesis. Here, we used a colorimetric product formation assay to screen a small-molecule library for the identification of potential inhibitors of SidA. Ebselen, an organoselenium compound, was identified as an inhibitor of SidA. This compound inhibited SidA with an IC50 value of 11 ± 1 μM. Ebselen derivative, ebsulfur, was also found to inhibit SidA with an IC50 value of 40 ± 13 μM. These compounds represent a new type of inhibitors of siderophore biosynthesis.

Department(s)

Arts, Languages, and Philosophy

Publication Status

Full Text Access

Keywords and Phrases

Aspergillus fumigatus; Drug discovery; Flavin-dependent monooxygenases; Siderophores

International Standard Serial Number (ISSN)

6183-1638; 0300-9084

Document Type

Article - Journal

Document Version

Citation

File Type

text

Language(s)

English

Rights

© 2026 Elsevier, All rights reserved.

Publication Date

01 Aug 2026

PubMed ID

42285434

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