Dark, rare and inspirational microbial matter in the extremobiosphere: 16 000 m of bioprospecting campaigns

The rationale of our bioprospecting campaigns is that the extremobiosphere, particularly the deep sea and hyper-arid deserts, harbours undiscovered biodiversity that is likely to express novel chemistry and biocatalysts thereby providing opportunities for therapeutic drug and industrial process development. We have focused on actinobacteria because of their frequent role as keystone species in soil ecosystems and their unrivaled track record as a source of bioactive compounds. Population numbers and diversity of actinobacteria in the extremobiosphere are traditionally considered to be low, although they often comprise the dominant bacterial biota. Recent metagenomic evaluation of ‘the uncultured microbial majority’ has now revealed enormous taxonomic diversity among ‘dark’ and ‘rare’ actinobacteria in samples as diverse as sediments from the depths of the Mariana Trench and soils from the heights of the Central Andes. The application of innovative culture and screening options that emphasize rigorous dereplication at each stage of the analysis, and strain prioritization to identify ‘gifted’ organisms, have been deployed to detect and characterize bioactive hit compounds and sought-after catalysts from this hitherto untapped resource. The rewards include first-in-a-class chemical entities with novel modes of action, as well as a growing microbial seed bank that represents a potentially enormous source of biotechnological and therapeutic innovation.