Biosensor-guided screening for macrolides.

Macrolides are complex polyketides of microbial origin that possess an extraordinary variety of pharmacological properties, paired with an impressive structural diversity. Bioassays for specific detection of such compounds will be of advantage for a class-specific drug screening. The current paper describes a cell-based microbial biosensor, assigning a luminescence response to natural or chemically modified macrolides, independent from their biological activity. This biosensor is based on the coupling of the structural luciferase genes of Vibrio fischeri to the regulatory control mechanism of a bacterial erythromycin resistance operon. The bioassays is easy to handle and can be applied to various screening formats. The feasibility of the test system for natural products screening is exemplified by the isolation and characterization of picromycin from a Streptomyces species. Biosensor-guided screening for macrolides is based on macrolide-promoted expression of lux genes and induction of luminescence (independent of macrolide antibiotic activity).