In depth natural product discovery - Myxobacterial strains that provided multiple secondary metabolites

Abstract

In recognition of many microorganisms ability to produce a variety of secondary metabolites in parallel, Zeeck and coworkers introduced the term "OSMAC" (one strain many compounds) around the turn of the century. Since then, additional efforts focused on the systematic characterization of a single bacterial species ability to form multiple secondary metabolite scaffolds. With the beginning of the genomic era mainly initiated by a dramatic reduction of sequencing costs, investigations of the genome encoded biosynthetic potential and especially the exploitation of biosynthetic gene clusters of undefined function gained attention. This was seen as a novel means to extend range and diversity of bacterial secondary metabolites. Genome analyses showed that even for well-studied bacterial strains, like the myxobacterium Myxococcus xanthus DK1622, many biosynthetic gene clusters are not yet assigned to their corresponding hypothetical secondary metabolites. In contrast to the results from emerging genome and metabolome mining techniques that show the large untapped biosynthetic potential per strain, many newly isolated bacterial species are still used for the isolation of only one target compound class and successively abandoned in the sense that no follow up studies are published from the same species. This work provides an overview about myxobacterial bacterial strains, from which not just one but multiple different secondary metabolite classes were successfully isolated. The underlying methods used for strain prioritization and natural product discovery such as biological characterization of crude extracts against a panel of pathogens, in-silico prediction of secondary metabolite abundance from genome data and state of the art instrumental analytics required for new natural product scaffold discovery in comparative settings are summarized and classified according to their output. Furthermore, for each approach selected studies performed with actinobacteria are shown to underline especially innovative methods used for natural product discovery.

Keywords: Actinobacteria; Bioactivity-guided isolation; Genome mining; Genomics; Myxobacteria; Natural products; Secondary metabolites; Secondary metabolomics.