Bioprospecting Soil Metagenomes for Antibiotics

Abstract

The recent emergence of antibiotic resistant pathogens, such as methicillin resistant Staphylococcus aureus (MRSA) and strains of multidrug resistant Mycobacterium tuberculosis, has raised awareness of a new class of global health threats. Unless alternative solutions are found, we can expect to see a considerable rise in incurable infection and fatality in developed and developing regions. Less than 10 % of the microbial natural product diversity has been explored and these uncultured communities have remained unexploited for pharmaceutical and biocatalytic applications. Soil contains the greatest diversity of bacteria compared to all other habitats. Thus the aim of this review is to explore the ways in which the uncultured majority of bacteria in soil has been explored and attempts made to exploit functional diversity using the extensive metagenomes of bacterial communities in soil. We focus on the capture of genes with metabolic potential to produce bioactive metabolites by a combination of approaches. These have involved (a) making metagenomic libraries in suitable expression hosts and examination of metabolic diversity by phenotypic screening, (b) co-culture, (c) sequence target PCR screening, (d) specialised metabolite analysis and (e) sequence analysis of the total assembled metagenome.