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    'Staff publications' is the digital repository of Wageningen University & Research

    'Staff publications' contains references to publications authored by Wageningen University staff from 1976 onward.

    Publications authored by the staff of the Research Institutes are available from 1995 onwards.

    Full text documents are added when available. The database is updated daily and currently holds about 240,000 items, of which 72,000 in open access.

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Record number 506284
Title The cyclochlorotine mycotoxin is produced by the nonribosomal peptide synthetase CctN in Talaromyces islandicus ('Penicillium islandicum')
Author(s) Schafhauser, Thomas; Kirchner, Norbert; Kulik, Andreas; Huijbers, Mieke M.E.; Flor, Liane; Caradec, Thibault; Fewer, David P.; Gross, Harald; Jacques, Philippe; Jahn, Linda; Jokela, Jouni; Leclère, Valérie; Ludwig-Müller, Jutta; Sivonen, Kaarina; Berkel, Willem J.H. van; Weber, Tilmann; Wohlleben, Wolfgang; Pée, Karl Heinz van
Source Environmental Microbiology 18 (2016)11. - ISSN 1462-2912 - p. 3728 - 3741.
DOI http://dx.doi.org/10.1111/1462-2920.13294
Department(s) Biochemistry
VLAG
Publication type Refereed Article in a scientific journal
Publication year 2016
Abstract

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.

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