The cyclochlorotine mycotoxin is produced by the nonribosomal peptide synthetase CctN in Talaromyces islandicus ('Penicillium islandicum')

Publikation: Beitrag in FachzeitschriftForschungsartikelBeigetragenBegutachtung


  • Thomas Schafhauser - , Eberhard Karls Universität Tübingen (Autor:in)
  • Norbert Kirchner - , Eberhard Karls Universität Tübingen (Autor:in)
  • Andreas Kulik - , Eberhard Karls Universität Tübingen (Autor:in)
  • Mieke M E Huijbers - , Wageningen University & Research (WUR) (Autor:in)
  • Liane Flor - , Professur für Allgemeine Biochemie (BC1) (Autor:in)
  • Thibault Caradec - , Université de Lille (Autor:in)
  • David P Fewer - , University of Helsinki (Autor:in)
  • Harald Gross - , Eberhard Karls Universität Tübingen (Autor:in)
  • Philippe Jacques - , Université de Lille (Autor:in)
  • Linda Jahn - , Professur für Pflanzenphysiologie (Autor:in)
  • Jouni Jokela - , University of Helsinki (Autor:in)
  • Valérie Leclère - , Université de Lille (Autor:in)
  • Jutta Ludwig-Müller - , Professur für Pflanzenphysiologie (Autor:in)
  • Kaarina Sivonen - , University of Helsinki (Autor:in)
  • Willem J H van Berkel - , Wageningen University & Research (WUR) (Autor:in)
  • Tilmann Weber - , Eberhard Karls Universität Tübingen (Autor:in)
  • Wolfgang Wohlleben - , Eberhard Karls Universität Tübingen (Autor:in)
  • Karl-Heinz van Pée - , Professur für Allgemeine Biochemie (BC1) (Autor:in)


Talaromyces islandicus ('Penicillium islandicum') is a widespread foodborne mold that produces numerous secondary metabolites, among them potent mycotoxins belonging to different chemical classes. A notable metabolite is the hepatotoxic and carcinogenic pentapeptide cyclochlorotine that contains the unusual amino acids β-phenylalanine, 2-aminobutyrate and 3,4-dichloroproline. Although the chemical structure has been known for over five decades, nothing is known about the biosynthetic pathway of cyclochlorotine. Bioinformatic analysis of the recently sequenced genome of T. islandicus identified a wealth of gene clusters potentially coding for the synthesis of secondary metabolites. Here, we show by RNA interference-mediated gene silencing that a nonribosomal peptide synthetase, CctN, is responsible for the synthesis of cyclochlorotine. Moreover, we identified novel cyclochlorotine chemical variants, whose production also depended on cctN expression. Surprisingly, the halogenase required for cyclochlorotine biosynthesis is not encoded in the cct cluster. Nonetheless, our findings enabled us to propose a detailed model for cyclochlorotine biosynthesis. In addition, comparative genomics revealed that cct-like clusters are present in all of the sequenced Talaromyces strains indicating a high prevalence of cyclochlorotine production ability.


Seiten (von - bis)3728-3741
FachzeitschriftEnvironmental Microbiology
PublikationsstatusVeröffentlicht - Nov. 2016

Externe IDs

Scopus 84976905121
ORCID /0000-0001-9147-4188/work/142257660



  • Fungal Proteins/genetics, Mycotoxins/biosynthesis, Penicillium/metabolism, Peptide Synthases/genetics, Peptides, Cyclic/biosynthesis, Phenylalanine/metabolism, Talaromyces/enzymology