MetaMiner: A Scalable Peptidogenomics Approach for Discovery of Ribosomal Peptide Natural Products With Blind Modifications From Microbial Communities

Liu Cao, Carnegie Mellon University
Alexey Gurevich, St. Petersburg State UniversityFollow
Kelsey L. Alexander, University of California, San Diego
C. Benjamin Naman, University of California, San Diego
Tiago Leão, University of California, San Diego
Evgenia Glukhov, University of California, San DiegoFollow
Tal Luzzatto-Knaan, University of California, San DiegoFollow
Fernando Vargas, University of California, San Diego
Robby Quinn, University of California, San Diego
Amina Bouslimani, University of California, San Diego
Louis Felix Nothias, University of California, San Diego
Nitin K. Singh, California Institute of Technology
Jon G. Sanders, University of California, San DiegoFollow
Rodolfo A.S. Benitez, University of California, San Diego
Luke R. Thompson, University of Southern MississippiFollow
Md-Nafiz Hamid, Iowa State UniversityFollow
James T. Morton, University of California, San DiegoFollow
Alla Mikheeno, St. Petersburg State University
Alexander Shlemov, St. Petersburg State University
Anton Korobeynikov, St. Petersburg State University
Iddo Friedberg, Iowa State UniversityFollow
Rob Knight, University of California, San DiegoFollow
Kasthuri Venkateswaran, California Institute of TechnologyFollow
William H. Gerwick, University of California, San DiegoFollow
Lena Gerwick, University of California, San DiegoFollow
Pieter C. Dorrestein, University of California, San DiegoFollow
Pavel A. Pevzner, University of California, San Diego
Hosein Mohimani, Carnegie Mellon UniversityFollow

Document Type

Article

Publication Date

12-18-2019

Department

Biological Sciences

School

Biological, Environmental, and Earth Sciences

Abstract

Ribosomally synthesized and post-translationally modified peptides (RiPPs) are an important class of natural products that contain antibiotics and a variety of other bioactive compounds. The existing methods for discovery of RiPPs by combining genome mining and computational mass spectrometry are limited to discovering specific classes of RiPPs from small datasets, and these methods fail to handle unknown post-translational modifications. Here, we present MetaMiner, a software tool for addressing these challenges that is compatible with large-scale screening platforms for natural product discovery. After searching millions of spectra in the Global Natural Products Social (GNPS) molecular networking infrastructure against just eight genomic and metagenomic datasets, MetaMiner discovered 31 known and seven unknown RiPPs from diverse microbial communities, including human microbiome and lichen microbiome, and microorganisms isolated from the International Space Station.

Publication Title

Cell Systems

Volume

9

Issue

6

First Page

600

Last Page

608

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