Abstract
NextGen microbial natural products discovery.
Highlights
Small-molecule secondary metabolites isolated from microorganisms and plants provide the chemical scaffolds of a large fraction of today’s pharmaceuticals
The number of sequenced microbial genome sequences is rapidly approaching 5000 sequenced genomes, of which a large majority is bacterial genomes with only a few hundred fungal genomes available. With this large number of sequences available, the question becomes ‘How does one most effectively search this vast sequence space for interesting natural products pathways?’ One approach commonly used is to focus on a few groups of bacteria of fungi known to produce bioactive natural products and comprehensively identify within their genomes natural products biosynthetic operons or gene cluster, and target the most diverse biosynthetic gene cluster for characterization
In the case that a strain is genetically tractable, gene disruption can be used to characterize biosynthetic gene functions. This ‘reverse discovery’ approach has been quite successfully used in genome-driven bioprospecting for a number of natural products identified in bacteria and some filamentous fungi (Lewis, 2013; Deane and Mitchell, 2014; Jensen et al, 2014)
Summary
Small-molecule secondary metabolites isolated from microorganisms and plants provide the chemical scaffolds of a large fraction of today’s pharmaceuticals. Driven by advances in sequencing, gene synthesis, bioinformatics and metabolomics, the natural products discovery process is beginning to undergo a major transformation – away from the tedious isolation, screening and dereplication process to in silico-based bioprospecting approaches that seek to eventually transform genomic information directly into biosynthetic outputs (Lewis, 2013; Deane and Mitchell, 2014).
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