Bioprospecting for antituberculosis leads from microbial metabolites

Covering: 2005 to 2010 Microbial metabolites have been an important source of tuberculosis (TB) therapeutics, but the last truly novel drug that was approved for the treatment of TB was discovered 40 years ago. In light of the growing threat of multi-drug resistance, recent advances have been made to accelerate the discovery rate of novel TB drugs including diversifying strategies for environmental strains, and high-throughput screening assays. This review will discuss the approaches used in biodiversity- and taxonomy-guided microbial natural product library construction, specific cell-based and target-based high-throughput screening assays and early-stage dereplication processes by liquid chromatography-mass spectrometry (LC-MS). New antituberculosis natural products that have been recently discovered are highlighted. In this review, we cover methods to bioprospect for microbial anti-TB leads, including construction of high-quality natural product libraries that are high in diversity and low in redundancy, high-throughput screening techniques, and analysis of novel structures.