Recent studies revealed numerous biosynthetic gene clusters (BGCs) across a wide range of bacterial and fungal species amenable to cultivation. However, little is known about the biosynthetic machinery and natural products produced by uncultivated organisms. I discuss the bottleneck of identifying BGCs coding for Peptidic Natural Products (PNPs) from metagenomics data and argue that the future progress in exploration of antibiotics critically depends on a transition from the current one-off process of PNP analysis to a high-throughput PNP discovery, including PNP discovery from metagenomics data. I further describe recent developments of metaSPAdes, truSPAdes, and 10XSPAdes assemblers that significantly increased the contig lengths and opened the door towards genome mining for PNPs in metagenomics datasets. Finally, I will describe recent advances in computational PNP discovery that span bioinformatics techniques ranging from metagenomics to genome mining to peptidogenomics.
