Single-bacterial genomics validates rich and varied specialized metabolism of uncultivated Entotheonella sponge symbionts

Tetsushi Mori, Jackson K.B. Cahn, Micheal C. Wilson, Roy A. Meoded, Vincent Wiebach, Ana Flávia Canovas Martinez, Eric J.N. Helfrich, Andreas Albersmeier, Daniel Wibberg, Steven Dätwyler, Ray Keren, Adi Lavy, Christian Rückert, Micha Ilan, Jörn Kalinowski, Shigeki Matsunaga, Haruko Takeyama, Jörn Piel*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

55 Citations (Scopus)


Marine sponges are prolific sources of unique bioactive natural products. The sponge Theonella swinhoei is represented by several distinct variants with largely nonoverlapping chemistry. For the Japanese chemotype Y harboring diverse complex polyketides and peptides, we previously provided genomic and functional evidence that a single symbiont, the filamentous, multicellular organism “Candidatus Entotheonella factor,” produces almost all of these compounds. To obtain further insights into the chemistry of “Entotheonella,” we investigated another phylotype, “Candidatus Entotheonella serta,” present in the T. swinhoei WA sponge chemotype, a source of theonellamide- and misakinolide-type compounds. Unexpectedly, considering the lower chemical diversity, sequencing of individual bacterial filaments revealed an even larger number of biosynthetic gene regions than for Ca. E. factor, with virtually no overlap. These included genes for misakinolide and theonellamide biosynthesis, the latter assigned by comparative genomic and metabolic analysis of a T. swinhoei chemotype from Israel, and by biochemical studies. The data suggest that both compound families, which were among the earliest model substances to study bacterial producers in sponges, originate from the same bacterium in T. swinhoei WA. They also add evidence that metabolic richness and variability could be a more general feature of Entotheonella symbionts.

Original languageEnglish
Pages (from-to)1718-1723
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number8
Publication statusPublished - 2018 Feb 20


  • Single-cell genomics
  • Sponges
  • Uncultivated bacteria

ASJC Scopus subject areas

  • General


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