Present and future outlooks on environmental DNA-based methods for antibiotic discovery

Abstract

Novel antibiotics are in constant demand to combat a global increase in antibiotic-resistant infections. Bacterial natural products have been a long-standing source of antibiotic compounds, and metagenomic mining of environmental DNA (eDNA) has increasingly provided new antibiotic leads. The metagenomic small-molecule discovery pipeline can be divided into three main steps: surveying eDNA, retrieving a sequence of interest, and accessing the encoded natural product. Improvements in sequencing technology, bioinformatic algorithms, and methods for converting biosynthetic gene clusters into small molecules are steadily increasing our ability to discover metagenomically encoded antibiotics. We predict that, over the next decade, ongoing technological improvements will dramatically increase the rate at which antibiotics are discovered from metagenomes.

Figure 1:

General pipelines for the discovery of metagenomically encoded natural products. (Top) A clone library mining approach using short read PCR screening and heterologous expression to access clusters of interest. (Bottom) Rapid mining approach applying long read sequencing and chemical synthesis.

Figure 2:

Selection of molecules highlighted in the review.