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Assay Development for High-Throughput Drug Screening Against Mycobacteria

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Biosensor-guided screening for macrolides.

V Möhrle¹, M Stadler, G Eberz

¹Bayer Technology Services GmbH, Leverkusen, Germany.

Analytical and Bioanalytical Chemistry

|May 15, 2007

Summary

A novel microbial biosensor detects macrolides, complex natural products, through luminescence. This tool aids drug screening by identifying macrolides regardless of their antibiotic activity.

Area of Science:

Microbiology
Biotechnology
Natural Products Chemistry

Background:

Macrolides are structurally diverse polyketides with significant pharmacological potential.
Efficient and specific detection methods are crucial for macrolide drug screening.
Existing bioassays may not cover the full structural diversity or activity spectrum of macrolides.

Purpose of the Study:

To develop a cell-based microbial biosensor for the class-specific detection of macrolides.
To create a screening tool that is independent of the biological activity of macrolides.
To demonstrate the utility of the biosensor in natural product discovery.

Main Methods:

Constructed a biosensor by linking Vibrio fischeri luciferase genes to an erythromycin resistance operon's regulatory elements.

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The biosensor generates a luminescence response upon exposure to macrolides, indicating their presence.

Utilized the biosensor for screening natural products from microbial sources.

Main Results:

The biosensor successfully detected both natural and chemically modified macrolides.
Luminescence response was independent of the macrolides' antibiotic activity.
Picromycin was isolated and characterized from a Streptomyces species using the biosensor-guided screening.

Conclusions:

The developed microbial biosensor offers a versatile and easy-to-handle platform for macrolide detection.
This biosensor facilitates drug screening and natural product discovery by enabling macrolide identification irrespective of bioactivity.
Biosensor-guided screening represents a powerful approach for identifying novel macrolide compounds.