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 KorobeynikovIddo Friedberg, Rob Knight, Kasthuri Venkateswaran, William H. Gerwick, Lena Gerwick, Pieter C. Dorrestein, Pavel A. Pevzner, Hosein Mohimani

Research output: Contribution to journalArticlepeer-review

Abstract

We have developed an efficient method for discovering ribosomally synthesized and post-translationally modified peptides with unknown post-translational modifications from microbial communities through the database search of mass spectra against peptides predicted by genome or metagenome mining. Searching eight datasets collected from various environments—including human microbiome, marine cyanobacteria, and International Space Station—resulted in the discovery of seven unknown RiPPs.

Original languageEnglish
Pages (from-to)600-608.e4
JournalCell Systems
Volume9
Issue number6
DOIs
StatePublished - 18 Dec 2019
Externally publishedYes

Bibliographical note

Funding Information:
The work of H.M. and L.C. was supported by a start-up fund from Carnegie Mellon University, a research fellowship from the Alfred P. Sloan Foundation, and a National Institutes of Health New Innovator Award DP2GM137413. The work of P.C.D. and P.A.P. was supported by NIH 2-P41-GM103484. P.C.D. is supported by GM097509. A.G. was supported by the Russian Science Foundation (grant 19-16-00049). A.M. was supported by St. Petersburg State University, Russia (grant ID PURE 28396291). A.S. and A.K. were supported by the Russian Science Foundation (grant 19-14-00172). T.L.-K. P.C.D. L.G. and W.H.G. were supported by NIH 2R01GM107550. L.G. and W.H.G. were supported by NIH R01GM118815. J.T.M. was funded by NSF GRFP DGE-1144086. We thank the implementation team of the Microbial Observatory (Microbial Tracking-1) project at NASA Ames Research Center and sample processing and isolation of microbes by Aleksandra Checinska Sielaff, JPL. Part of the research described in this publication was performed at the Jet Propulsion Laboratory, California Institute of Technology, under a contract with NASA. The work of N.K.S. and K.V. was funded by NASA 19-12829-26 and 19-12829-27. C.B.N. was supported by postdoctoral fellowship from NCI/NIH Training Program in the Biochemistry of Growth Regulation and Oncogenesis (T32 CA009523). T.L.-K was supported by Vaadia-BARD Postdoctoral fellowship award no. FI-494-13. T.L. was supported by CAPES Foundation for Research fellowship (13425-13-7). The work of I.F. was supported, in part, by NSF awards ABI-1551363 and ABI-1458359. H.M. P.A.P. P.C.D. L.G. W.H.G. K.V. R.K. and I.F. designed and directed the study. H.M. P.A.P. and L.C. wrote the paper. L.C. A.G. A.M. A.S. A.K. M.-N.H. and J.T.M. wrote the codes. K.L.A. and C.B.N. conducted the NMR experiment. T.L. E.G. T.L.-K. F.V. R.Q. A.B. L.F.N. N.K.S. J.G.S. R.A.S.B. and L.R.T. collected samples, liquid chromatography-tandem mass spectrometry, and metagenomic data. The work of W.H.G. was supported by the University of California, San Diego, Scripps Institution of Oceanography, and a grant from the NIH (Award GM118815). W.H.G. has an equity interest in Sirenas Marine Discovery, a company that may potentially benefit from the research results, and also serves on the company's Scientific Advisory Board. The terms of this arrangement have been reviewed and approved by the University of California, San Diego, in accordance with its conflict of interest policies. The work of P.A.P. was supported by the US National Institutes of Health grant 2-P41-GM103484. P.A.P. has an equity interest and receives income from Digital Proteomics, a company that may potentially benefit from the research results. The terms of this arrangement have been reviewed and approved by the University of California, San Diego, in accordance with its conflict of interest policies.

Funding Information:
The work of W.H.G. was supported by the University of California, San Diego, Scripps Institution of Oceanography, and a grant from the NIH (Award GM118815). W.H.G. has an equity interest in Sirenas Marine Discovery, a company that may potentially benefit from the research results, and also serves on the company’s Scientific Advisory Board. The terms of this arrangement have been reviewed and approved by the University of California, San Diego, in accordance with its conflict of interest policies. The work of P.A.P. was supported by the US National Institutes of Health grant 2-P41-GM103484. P.A.P. has an equity interest and receives income from Digital Proteomics, a company that may potentially benefit from the research results. The terms of this arrangement have been reviewed and approved by the University of California, San Diego, in accordance with its conflict of interest policies.

Funding Information:
The work of H.M. and L.C. was supported by a start-up fund from Carnegie Mellon University , a research fellowship from the Alfred P. Sloan Foundation, and a National Institutes of Health New Innovator Award DP2GM137413 . The work of P.C.D. and P.A.P. was supported by NIH 2-P41-GM103484 . P.C.D. is supported by GM097509 . A.G. was supported by the Russian Science Foundation (grant 19-16-00049 ). A.M. was supported by St. Petersburg State University , Russia (grant ID PURE 28396291 ). A.S. and A.K. were supported by the Russian Science Foundation (grant 19-14-00172 ). T.L.-K., P.C.D., L.G., and W.H.G. were supported by NIH 2R01GM107550 . L.G. and W.H.G. were supported by NIH R01GM118815 . J.T.M. was funded by NSF GRFP DGE-1144086 . We thank the implementation team of the Microbial Observatory (Microbial Tracking-1) project at NASA Ames Research Center and sample processing and isolation of microbes by Aleksandra Checinska Sielaff, JPL. Part of the research described in this publication was performed at the Jet Propulsion Laboratory, California Institute of Technology, under a contract with NASA. The work of N.K.S. and K.V. was funded by NASA 19-12829-26 and 19-12829-27 . C.B.N. was supported by postdoctoral fellowship from NCI /NIH Training Program in the Biochemistry of Growth Regulation and Oncogenesis ( T32 CA009523 ). T.L.-K was supported by Vaadia-BARD Postdoctoral fellowship award no. FI-494-13. T.L. was supported by CAPES Foundation for Research fellowship ( 13425-13-7 ). The work of I.F. was supported, in part, by NSF awards ABI-1551363 and ABI-1458359 .

Publisher Copyright:
© 2019 Elsevier Inc.

Keywords

  • computational mass spectrometry
  • metagenomics
  • microbial metabolites
  • natural products discovery
  • ribosomally synthesized and post-translationally modified peptides

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Histology
  • Cell Biology

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