What question did this study set out to answer?

This research aims to find natural-product inhibitors targeting key enzymes in the MEP pathway to combat antibiotic resistance.

March 16, 2026Open Access

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

Key Points

This research aims to find natural-product inhibitors targeting key enzymes in the MEP pathway to combat antibiotic resistance.
Screened natural-product libraries against Mycobacterium tuberculosis DXPS and Escherichia coli IspD.
Utilized crystal structures for understanding binding modes of potential inhibitors.
Identified specific natural products from myxobacteria and Streptomyces.
Discovered maracen A from myxobacteria as an inhibitor of DXPS.
Identified polyketomycin from Streptomyces as a potential IspD inhibitor.
These findings propose new avenues for antibiotic development against resistant bacteria.

Abstract

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.

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

Key Points

Abstract

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