Genome of Diaporthe sp. provides insights into the potential inter-phylum transfer of a fungal sesquiterpenoid biosynthetic pathway

Jose Guedes de Sena Filho, Maureen B. Quin, Daniel J. Spakowicz, Jeffrey J. Shaw, Kaury Kucera, Brian Dunican, Scott A. Strobel, Claudia Schmidt-Dannert

Research output: Contribution to journalArticlepeer-review

2 Scopus citations

Abstract

Fungi have highly active secondary metabolic pathways which enable them to produce a wealth of sesquiterpenoids that are bioactive. One example is Δ6-protoilludene, the precursor to the cytotoxic illudins, which are pharmaceutically relevant as anticancer therapeutics. To date, this valuable sesquiterpene has only been identified in members of the fungal division Basidiomycota. To explore the untapped potential of fungi belonging to the division Ascomycota in producing Δ6-protoilludene, we isolated a fungal endophyte Diaporthe sp. BR109 and show that it produces a diversity of terpenoids including Δ6-protoilludene. Using a genome sequencing and mining approach 17 putative novel sesquiterpene synthases were identified in Diaporthe sp. BR109. A phylogenetic approach was used to predict which gene encodes Δ6-protoilludene synthase, which was then confirmed experimentally. These analyses reveal that the sesquiterpene synthase and its putative sesquiterpene scaffold modifying cytochrome P450(s) may have been acquired by inter-phylum horizontal gene transfer from Basidiomycota to Ascomycota. Bioinformatic analyses indicate that inter-phylum transfer of these minimal sequiterpenoid secondary metabolic pathways may have occurred in other fungi. This work provides insights into the evolution of fungal sesquiterpenoid secondary metabolic pathways in the production of pharmaceutically relevant bioactive natural products.

Original languageEnglish (US)
Pages (from-to)1050-1063
Number of pages14
JournalFungal Biology
Volume120
Issue number8
DOIs
StatePublished - Aug 1 2016

Bibliographical note

Funding Information:
Financial support was provided by Empresa Brasileira de Pesquisa Agropecuaria – EMBRAPA Authorizaton code: 02001.005069/2011-14 (to JGSF), the National Institutes of Health Grant GM080299 (to C.S-D.), and Office of Assistant Secretary of Defense for Research and Engineering NSSEFF Grant N00244-09-1-0070 (to SAS). DJS was supported by the NIH T15 LM007056-29 .

Publisher Copyright:
© 2016 British Mycological Society

Keywords

  • Anticancer
  • Ascomycota
  • Biosynthesis
  • Evolution
  • Natural products
  • Sesquiterpene synthase

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