Natural Product Isolation and Characterization: Gene-independent Approaches

Abstract

Three eras can be defined in the history of natural product isolation and characterization for activity. Pre-1800, biologically active potions and impure infusions were the norm. In the 19th and 20th centuries pure molecules were isolated and structures determined without recourse to biosynthetic gene cluster information. In the post-genomic era of the 21st century, bioinformatics and genome mining drive much of the decisions about which producer organisms to investigate. Single-molecule X-ray analysis was crucial in the 1970s and 1980s for determination of complex molecular frameworks, but has been largely superseded by modern NMR, mass spectrometry approaches, and micro-electron diffraction techniques on nanocrystals. Observations that changing culture conditions in fungal and bacterial fermentations could radically alter the number and composition of natural products led to the concept of one strain many compounds, which prefigured genome sequencing results that have turned up 20–30 biosynthetic gene clusters in microbial producers, many of which are silent, under defined laboratory culture conditions.