Mushroom hunting by using bioinformatics: Application of a predictive framework facilitates the selective identification of sesquiterpene synthases in Basidiomycota

Maureen B. Quin, Christopher M. Flynn, Grayson T. Wawrzyn, Swati Choudhary, Claudia Schmidt-Dannert

Research output: Contribution to journalArticle

26 Scopus citations

Abstract

The Basidiomycota fungi represent a diverse source of natural products, particularly the sesquiterpenoids. Recently, genome sequencing, genome mining, and the subsequent discovery of a suite of sesquiterpene synthases in Omphalotus olearius was described. A predictive framework was developed to facilitate the discovery of sesquiterpene synthases in Basidiomycota. Phylogenetic analyses indicated a conservation of both sequence and initial cyclization mechanisms used. Here, the first robust application of this predictive framework is reported. It was used to selectively identify sesquiterpene synthases that follow 1,6-, 1,10-, and 1,11-cyclization mechanisms in the crust fungus Stereum hirsutum. The successful identification and characterization of a 1,6- and a 1,10-cyclizing sesquiterpene synthase, as well as three 1,11-cyclizing Δ6-protoilludene synthases, is described. This study verifies the accuracy and utility of the predictive framework as a roadmap for the discovery of specific sesquiterpene synthases from Basidiomycota, and thus represents an important step forward in natural product discovery. Ringing up: Several putative sesquiterpene synthases from Stereum hirsutum have been discovered through phylogenetic analyses. Clustering based on sequence conservation and shared cyclization mechanisms allows the directed isolation and characterization of 1,6-, 1,10- and 1,11-cyclizing enzymes. Three new Δ6-protoilludene synthases are described and kinetically characterized.

Original languageEnglish (US)
Pages (from-to)2480-2491
Number of pages12
JournalChemBioChem
Volume14
Issue number18
DOIs
StatePublished - Dec 2013

Keywords

  • GC/MS
  • anticancer agents
  • biosynthesis
  • kinetics
  • natural products

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