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

Autor:	Schafhauser T; Mikrobiologie und Biotechnologie, Interfakultäres Institut für Mikrobiologie und Infektionsmedizin, Eberhard Karls Universität Tübingen, Auf der Morgenstelle 28, 72076, Tübingen, Germany., Kirchner N; Department of Pharmaceutical Biology, Pharmaceutical Institute, University of Tübingen, Auf der Morgenstelle 8, 72076, Tübingen, Germany.; German Centre for Infection Research (DZIF), Partner site Tübingen, 72076, Tübingen, Germany., Kulik A; Mikrobiologie und Biotechnologie, Interfakultäres Institut für Mikrobiologie und Infektionsmedizin, Eberhard Karls Universität Tübingen, Auf der Morgenstelle 28, 72076, Tübingen, Germany., Huijbers MM; Laboratory of Biochemistry, Wageningen University, Dreijenlaan 3, 6703, HA Wageningen, The Netherlands., Flor L; Allgemeine Biochemie, Technische Universität Dresden, 01069, Dresden, Germany., Caradec T; Research Laboratory in Agro-Food and Biotechnology, Charles Viollette Institute, Team ProBioGEM, Polytech-Lille, Université Lille1- Sciences et Technologies, 59655 Villeneuve d'Ascq, France., Fewer DP; Microbiology and Biotechnology Division, Department of Food and Environmental Sciences, University of Helsinki, Viikinkaari 9, FIN-00014, Helsinki, Finland., Gross H; Department of Pharmaceutical Biology, Pharmaceutical Institute, University of Tübingen, Auf der Morgenstelle 8, 72076, Tübingen, Germany.; German Centre for Infection Research (DZIF), Partner site Tübingen, 72076, Tübingen, Germany., Jacques P; Research Laboratory in Agro-Food and Biotechnology, Charles Viollette Institute, Team ProBioGEM, Polytech-Lille, Université Lille1- Sciences et Technologies, 59655 Villeneuve d'Ascq, France., Jahn L; Institut für Botanik, Technische Universität Dresden, 01062, Dresden, Germany., Jokela J; Microbiology and Biotechnology Division, Department of Food and Environmental Sciences, University of Helsinki, Viikinkaari 9, FIN-00014, Helsinki, Finland., Leclère V; Research Laboratory in Agro-Food and Biotechnology, Charles Viollette Institute, Team ProBioGEM, Polytech-Lille, Université Lille1- Sciences et Technologies, 59655 Villeneuve d'Ascq, France., Ludwig-Müller J; Institut für Botanik, Technische Universität Dresden, 01062, Dresden, Germany., Sivonen K; Microbiology and Biotechnology Division, Department of Food and Environmental Sciences, University of Helsinki, Viikinkaari 9, FIN-00014, Helsinki, Finland., van Berkel WJ; Laboratory of Biochemistry, Wageningen University, Dreijenlaan 3, 6703, HA Wageningen, The Netherlands., Weber T; Mikrobiologie und Biotechnologie, Interfakultäres Institut für Mikrobiologie und Infektionsmedizin, Eberhard Karls Universität Tübingen, Auf der Morgenstelle 28, 72076, Tübingen, Germany.; German Centre for Infection Research (DZIF), Partner site Tübingen, 72076, Tübingen, Germany.; The Novo Nordisk Foundation Center for Biosustainability, Technical University of Denmark, Kogle Alle 6, 2970, Hørsholm, Denmark., Wohlleben W; Mikrobiologie und Biotechnologie, Interfakultäres Institut für Mikrobiologie und Infektionsmedizin, Eberhard Karls Universität Tübingen, Auf der Morgenstelle 28, 72076, Tübingen, Germany.; German Centre for Infection Research (DZIF), Partner site Tübingen, 72076, Tübingen, Germany., van Pée KH; Allgemeine Biochemie, Technische Universität Dresden, 01069, Dresden, Germany.
Jazyk:	angličtina
Zdroj:	Environmental microbiology [Environ Microbiol] 2016 Nov; Vol. 18 (11), pp. 3728-3741. Date of Electronic Publication: 2016 Jun 27.
DOI:	10.1111/1462-2920.13294
Abstrakt:	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. (© 2016 Society for Applied Microbiology and John Wiley & Sons Ltd.)
Databáze:	MEDLINE
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