Technology’s Big Impact on Microbial Small-Molecule Research

With many emerging technologies at hand, there is a growing sense of anticipation for a second “golden-age” of microbial natural products drug discovery.  Leading this charge have been considerable advances in the field molecular biology that have made genomic and metagenomic approaches more accessible to the scientific and industrial communities.  In parallel to these efforts, developments in robotics, mass spectrometry, and cell imaging are creating new opportunities for transforming the study of microbial-derived small molecules in exciting ways.  Highly adaptable robotics platforms are now becoming more accessible enabling researchers to improve sample throughput and processing accuracy.  Using these types of tools, our group has developed new co-culture strategies that achieve a more representative portrayal of an organism’s natural environment, as well as enable the rapid screening of a multitude of strain-specific interactions in a microscale (microtiter) format.  These studies are supported by a rapid mass spectrometry imaging technology (LAESI MS) that affords critical insights to the chemical interplay among neighboring microbes.  Novel phenotypic approaches to bioactivity testing employing high content screening methods are also enhancing the detection of complex biological phenomena.  These approaches are opening access to the study of new disease areas by providing adaptable platforms for assay development.  Examples of these techniques and their integration into the bioactive natural product discovery process will be discussed along with an outlook toward the overall impact these techniques will have on small-molecule drug discovery.