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Updated: Aug 11, 2026

Metabolic Profiling to Determine Bactericidal or Bacteriostatic Effects of New Natural Products using Isothermal Microcalorimetry
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Published on: October 29, 2020

The Natural Product Corramycin Acts as a DNA Gyrase Poison and Overcomes Fluoroquinolone Resistance in Mycobacterium

Franziska Fries1,2, Jennifer Herrmann1,2, Michael Dal Molin3,4,5

  • 1Helmholtz Institute for Pharmaceutical Research Saarland (HIPS), Helmholtz Centre for Infection Research (HZI) and Department of Pharmacy, Saarland University, Saarbrücken, Germany.

Advanced Science (Weinheim, Baden-Wurttemberg, Germany)
|August 10, 2026
PubMed

Insights

Corramycin, a novel natural product, shows potent activity against drug-susceptible and -resistant tuberculosis strains. It works by uniquely inhibiting DNA gyrase, offering a promising new approach to combatting antimicrobial resistance.

Area of Science:

  • Microbiology
  • Natural Product Chemistry
  • Drug Discovery

Background:

  • Tuberculosis remains a leading global infectious disease, with rising multidrug-resistant strains necessitating novel antibiotics.
  • Existing treatments face challenges due to resistance, highlighting the urgent need for new therapeutic strategies with distinct mechanisms of action.

Purpose of the Study:

  • To identify and characterize novel antitubercular compounds from natural sources.
  • To investigate the mechanism of action and structural basis for the activity of corramycin against Mycobacterium tuberculosis.

Main Methods:

  • Screening of a myxobacterial extract library for antitubercular activity.
  • Determination of corramycin's mechanism of action, including its effect on DNA gyrase.
  • Cryo-electron microscopy to elucidate the structural complex of Mycobacterium tuberculosis gyrase and corramycin.

Main Results:

  • Corramycin exhibits potent bactericidal activity against both drug-sensitive and multidrug-resistant Mycobacterium tuberculosis strains.
  • Corramycin induces DNA double-strand breaks by a novel mechanism of DNA gyrase poisoning.
  • Structural analysis reveals corramycin binds to a unique site on DNA gyrase, distinct from fluoroquinolones, overcoming existing resistance.

Conclusions:

  • Corramycin is a promising natural product with potent antitubercular activity and a novel mechanism of action.
  • Its ability to overcome fluoroquinolone resistance makes it a valuable scaffold for developing new antibiotics against tuberculosis.
  • This discovery offers a potential new avenue to address the global crisis of antimicrobial resistance.
Keywords:
DNA synthesis inhibitorMycobacterium tuberculosiscryo‐EMgyrase poisonmechanism of actionnatural products

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