Large-scale metagenomic natural product discovery from complex environments.

Natural product reseach has generally been limited to metabolites isolated from easily cultivated organisms and systems which are highly expressed. Due to advances in next-generation sequencing, data analysis, and genetic engineering, it is now possible to routinely identify and express a wide range of natural product gene clusters from virtually any source. Complex environments such as soil, however, pose unique challenges in terms of gaining access to natural product chemical diversity. These challenges stem from the immense diversity found in soils which renders standard NGS and genetic engineering efforts ineffective.

Here, we describe several technological advances which help to overcome barriers in metagenomic natural product discovery. The purpose of our platform is to enable large-scale antimicrobial discovery but the concepts and strategy can be applied to support general natural product research as well.