Mining the microbial metabolome: a new frontier for natural product lead discovery

Traditionally, natural products have been important sources of new leads for the pharmaceutical industry [1], but with discovery rates of novel structural classes in decline [2], the need to bioprospect alternate sources of chemical diversity is evident. Microbial genome sequencing projects have revealed the presence of 'silent' biosynthetic gene clusters where there is no current detectable product [3]. Likewise, culture-independent techniques have provided access to the collective genomes of environmental microflora [4]. Both sources of molecular diversity could encode potentially valuable metabolites. The ability to measure the entire complement of metabolites within microorganisms that are used as surrogate hosts to express such gene clusters will be crucial to the exploitation of these yet untapped reservoirs of metabolic diversity for future natural product drug discovery.