Identification of Natural-Product Inhibitors of the 2 C -Methyl- d -erythritol 4-Phosphate Pathway

ACS Medicinal Chemistry Letters 2026 Open access

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Authors: Eleonora Diamanti, Alaa Alhayek, Antoine Lacour, Mohammad Walid Shahrour, Daan Willocx, Boris A. Illarionov, Markus Fischer, Marc Stadler, Norbert Reiling, Jennifer E. Herrmann, R. P. A. Müller, Anna K. H. Hirsch
DOI: 10.1021/acsmedchemlett.6c00054
Cited by: 0
References: 28

Abstract

High Resolution Image Download MS PowerPoint Slide To tackle the emerging resistance against existing antibiotics, we screened natural-product (NP) libraries against two underexploited target enzymes from the 2 C -methyl- d -erythritol 4-phosphate (MEP) pathway, namely, Mycobacterium tuberculosis DXPS and Escherichia coli IspD. We have chosen these two enzymes due to the availability of the crystal structures that helped to elucidate the putative binding modes of the NPs identified. The screening of a NP collection led to the discovery of myxobacteria-derived maracen A and Streptomyces-derived polyketomycin as the first NPs targeting these enzymes.

Fields of Study & Subjects

Microbial Natural Products and Biosynthesis Bioactive natural compounds Plant biochemistry and biosynthesis

Publication details

Journal / source
ACS Medicinal Chemistry Letters
Volume
17
Issue
4
Pages
909–915
Publication date
13 March 2026
Language
EN