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

Liu Cao; Alexey Gurevich; Kelsey L Alexander; C Benjamin Naman; Tiago Leão; Evgenia Glukhov; Tal Luzzatto-Knaan; Fernando Vargas; Robby Quinn; Amina Bouslimani; Louis Felix Nothias; Nitin K Singh; Jon G Sanders; Rodolfo A S Benitez; Luke R Thompson; Md-Nafiz Hamid; James T Morton; Alla Mikheenko; Alexander Shlemov; Anton Korobeynikov; Iddo Friedberg; Rob Knight; Kasthuri Venkateswaran; William H Gerwick; Lena Gerwick; Pieter C Dorrestein; Pavel A Pevzner; Hosein Mohimani

doi:10.1016/j.cels.2019.09.004

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

Cell Syst. 2019 Dec 18;9(6):600-608.e4. doi: 10.1016/j.cels.2019.09.004. Epub 2019 Oct 16.

Authors

Liu Cao¹, Alexey Gurevich², Kelsey L Alexander³, C Benjamin Naman⁴, Tiago Leão⁵, Evgenia Glukhov⁵, Tal Luzzatto-Knaan⁶, Fernando Vargas⁶, Robby Quinn⁶, Amina Bouslimani⁶, Louis Felix Nothias⁶, Nitin K Singh⁷, Jon G Sanders⁸, Rodolfo A S Benitez⁸, Luke R Thompson⁹, Md-Nafiz Hamid¹⁰, James T Morton¹¹, Alla Mikheenko², Alexander Shlemov², Anton Korobeynikov¹², Iddo Friedberg¹⁰, Rob Knight¹³, Kasthuri Venkateswaran⁷, William H Gerwick⁵, Lena Gerwick⁵, Pieter C Dorrestein¹⁴, Pavel A Pevzner¹⁵, Hosein Mohimani¹⁶

Affiliations

¹ Computational Biology Department, Carnegie Mellon University, Pittsburgh, PA, USA.
² Center for Algorithmic Biotechnology, Institute of Translational Biomedicine, St. Petersburg State University, St. Petersburg, Russia.
³ Center for Marine Biotechnology and Biomedicine, Scripps Institution of Oceanography and Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California, San Diego, San Diego, CA, USA; Department of Chemistry and Biochemistry, University of California, San Diego, San Diego, CA, USA.
⁴ Center for Marine Biotechnology and Biomedicine, Scripps Institution of Oceanography and Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California, San Diego, San Diego, CA, USA; Li Dak Sum Yip Yio Chin Kenneth Li Marine Biopharmaceutical Research Center, Department of Marine Pharmacy, College of Food and Pharmaceutical Sciences, Ningbo University, Ningbo, Zhejiang, China.
⁵ Center for Marine Biotechnology and Biomedicine, Scripps Institution of Oceanography and Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California, San Diego, San Diego, CA, USA.
⁶ Collaborative Mass Spectrometry Innovation Center, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California, San Diego, San Diego, CA, USA.
⁷ Jet Propulsion Laboratory, California Institute of Technology, Pasadena, CA, USA.
⁸ Department of Pediatrics, University of California, San Diego School of Medicine, San Diego, CA, USA.
⁹ Department of Biological Sciences and Northern Gulf Institute, University of Southern Mississippi, Hattiesburg, MS, USA; Ocean Chemistry and Ecosystems Division, Atlantic Oceanographic and Meteorological Laboratory, National Oceanic and Atmospheric Administration, stationed at Southwest Fisheries Science Center, La Jolla, CA, USA.
¹⁰ Department of Veterinary Microbiology and Preventive Medicine, Iowa State University, Ames, IA, USA; Interdepartmental program in Bioinformatics and Computational Biology, Iowa State University, Ames, IA, USA.
¹¹ Department of Pediatrics, University of California, San Diego School of Medicine, San Diego, CA, USA; Department of Computer Science and Engineering, University of California, San Diego, San Diego, CA, USA.
¹² Center for Algorithmic Biotechnology, Institute of Translational Biomedicine, St. Petersburg State University, St. Petersburg, Russia; Department of Mathematics and Mechanics, St. Petersburg State University, St. Petersburg, Russia.
¹³ Department of Pediatrics, University of California, San Diego School of Medicine, San Diego, CA, USA; Department of Computer Science and Engineering, University of California, San Diego, San Diego, CA, USA; Center for Microbiome Innovation, Jacobs School of Engineering, University of California San Diego, San Diego, CA, USA; Department of Bioengineering, University of California, San Diego, San Diego, CA, USA.
¹⁴ Collaborative Mass Spectrometry Innovation Center, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California, San Diego, San Diego, CA, USA; Center for Microbiome Innovation, Jacobs School of Engineering, University of California San Diego, San Diego, CA, USA.
¹⁵ Department of Computer Science and Engineering, University of California, San Diego, San Diego, CA, USA; Center for Microbiome Innovation, Jacobs School of Engineering, University of California San Diego, San Diego, CA, USA.
¹⁶ Computational Biology Department, Carnegie Mellon University, Pittsburgh, PA, USA; Department of Computer Science and Engineering, University of California, San Diego, San Diego, CA, USA. Electronic address: hoseinm@andrew.cmu.edu.

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.

Keywords: computational mass spectrometry; metagenomics; microbial metabolites; natural products discovery; ribosomally synthesized and post-translationally modified peptides.

Publication types

Research Support, N.I.H., Extramural
Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

Computational Biology / methods*
Genomics / methods
Humans
Microbiota / genetics*
Peptides / chemistry
Protein Processing, Post-Translational / genetics*
Ribosomes / genetics
Software

Substances

Peptides

Abstract

Publication types

MeSH terms

Substances

Grants and funding