A multiproducer microbiome generates chemical diversity in the marine sponge Mycale hentscheli

Michael Rust, Eric J.N. Helfrich, Michael F. Freeman, Pakjira Nanudorn, Christopher M. Field, Christian Rückert, Tomas Kündig, Michael J. Page, Victoria L. Webb, Jörn Kalinowski, Shinichi Sunagawa, Jörn Piel

Research output: Contribution to journalArticlepeer-review

11 Scopus citations

Abstract

Bacterial specialized metabolites are increasingly recognized as important factors in animal–microbiome interactions: for example, by providing the host with chemical defenses. Even in chemically rich animals, such compounds have been found to originate from individual members of more diverse microbiomes. Here, we identified a remarkable case of a moderately complex microbiome in the sponge host Mycale hentscheli in which multiple symbionts jointly generate chemical diversity. In addition to bacterial pathways for three distinct polyketide families comprising microtubule-inhibiting peloruside drug candidates, mycalamide-type contact poisons, and the eukaryotic translation-inhibiting pateamines, we identified extensive biosynthetic potential distributed among a broad phylogenetic range of bacteria. Biochemical data on one of the orphan pathways suggest a previously unknown member of the rare polytheonamide-type cytotoxin family as its product. Other than supporting a scenario of cooperative symbiosis based on bacterial metabolites, the data provide a rationale for the chemical variability of M. hentscheli and could pave the way toward biotechnological peloruside production. Most bacterial lineages in the compositionally unusual sponge microbiome were not known to synthesize bioactive metabolites, supporting the concept that microbial dark matter harbors diverse producer taxa with as yet unrecognized drug discovery potential.

Original languageEnglish (US)
Pages (from-to)9508-9518
Number of pages11
JournalProceedings of the National Academy of Sciences of the United States of America
Volume117
Issue number17
DOIs
StatePublished - Apr 28 2020

Bibliographical note

Funding Information:
This project has received funding from ETH Research Grant ETH-26 17-1, Swiss National Science Foundation Grants 205321 and 205320, and the European Research Council under the European Union?s Horizon 2020 Research and Innovation Programme Grant 742739 and the Helmut Horten Foundation. J.P. is grateful for an Investigator Grant of the Gordon and Betty Moore Foundation. P.N. was supported by a Swiss Government Excellence Scholarship. We thank the Functional Genomics Center Zurich for Illumina sequencing. We also thank M. Korneli for the construction of the pCDFBAD-Myc-HisA expression vector and A. Bhushan for providing the pCDFBAD-aerD plasmid.

Funding Information:
ACKNOWLEDGMENTS. This project has received funding from ETH Research Grant ETH-26 17-1, Swiss National Science Foundation Grants 205321 and 205320, and the European Research Council under the European Union’s Horizon 2020 Research and Innovation Programme Grant 742739 and the Helmut Horten Foundation. J.P. is grateful for an Investigator Grant of the Gordon and Betty Moore Foundation. P.N. was supported by a Swiss Government Excellence Scholarship. We thank the Functional Genomics Center Zurich for Illumina sequencing. We also thank M. Korneli for the construction of the pCDFBAD-Myc-HisA expression vector and A. Bhushan for providing the pCDFBAD-aerD plasmid.

Publisher Copyright:
© 2020 National Academy of Sciences. All rights reserved.

Keywords

  • Biosynthesis
  • Symbiosis
  • sponges
  • | microbiomes
  • | natural products

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