Identification of Natural-Product Inhibitors of the 2 <i>C</i> -Methyl- <scp>d</scp> -erythritol 4-Phosphate Pathway
To tackle the emerging resistance against existing antibiotics, we screened natural-product (NP) libraries against two underexploited target enzymes from the 2C-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.
Authors
- Daan Willocx (ORCID: https://orcid.org/0000-0001-6990-8349)
- Johannes M. Herrmann (ORCID: https://orcid.org/0000-0003-2081-4506)
- Alaa Alhayek (ORCID: https://orcid.org/0000-0001-8192-6574)
- Norbert Reiling (ORCID: https://orcid.org/0000-0001-6673-4291)
- Eleonora Diamanti (ORCID: https://orcid.org/0000-0001-8392-5575)
- Boris Illarionov (ORCID: https://orcid.org/0009-0007-8489-0651)
- R. P. A. Müller
- Antoine Lacour
- Anna K. H. Hirsch (ORCID: https://orcid.org/0000-0001-8734-4663)
- Mohammad Walid Shahrour
- Markus Fischer
- Marc Stadler
Institutions
- MSH Medical School Hamburg – University of Applied Sciences and Medical University (DE)
- German Center for Infection Research (DE)
- Helmholtz Centre for Infection Research (DE)
- Research Center Borstel - Leibniz Lung Center (DE)
- Helmholtz Institute for Pharmaceutical Research Saarland (DE)
- Saarland University (DE)
Publication Details
- Journal
- ACS Medicinal Chemistry Letters
- Published
- 2026-03-13
- DOI
- https://doi.org/10.1021/acsmedchemlett.6c00054
- Primary Topic
- Plant biochemistry and biosynthesis
- Type
- article
- Field-Weighted Citation Impact
- 0.00