Recent analyses of public microbial genomes have found over a million biosynthetic gene clusters, the natural products of the majority of which remain unknown. Additionally, GNPS harbors billions of mass spectra of natural products without known structures and biosynthetic genes. We bridge the gap between large-scale genome mining and mass spectral datasets for natural product discovery by developing HypoRiPPAtlas, an Atlas of hypothetical natural product structures, which is ready-to-use for in silico database search of tandem mass spectra. HypoRiPPAtlas is constructed by mining genomes using seq2ripp, a machine-learning tool for the prediction of ribosomally synthesized and post-translationally modified peptides (RiPPs). In HypoRiPPAtlas, we identify RiPPs in microbes and plants. HypoRiPPAtlas could be extended to other natural product classes in the future by implementing corresponding biosynthetic logic. This study paves the way for large-scale explorations of biosynthetic pathways and chemical structures of microbial and plant RiPP classes.
Even in the genomic era, microbial natural product discovery workflows can be laborious and limited in their ability to target molecules with specific structural features. Here we leverage an understanding of biosynthesis to develop a workflow that targets the discovery of alkyl halide-derived natural products by depleting halide anions, a key biosynthetic substrate for enzymatic halogenation, from microbial growth media. By comparing the metabolomes of bacterial cultures grown in halide-replete and deficient media, we rapidly discovered the nostochlorosides, the products of an orphan halogenase-encoding gene cluster from
- NSF-PAR ID:
- 10485616
- Publisher / Repository:
- Nature Publishing Group
- Date Published:
- Journal Name:
- Nature Chemistry
- Volume:
- 16
- Issue:
- 2
- ISSN:
- 1755-4330
- Format(s):
- Medium: X Size: p. 173-182
- Size(s):
- p. 173-182
- Sponsoring Org:
- National Science Foundation
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