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

Authors :
Schafhauser T
Kirchner N
Kulik A
Huijbers MM
Flor L
Caradec T
Fewer DP
Gross H
Jacques P
Jahn L
Jokela J
Leclère V
Ludwig-Müller J
Sivonen K
van Berkel WJ
Weber T
Wohlleben W
van Pée KH
Source :
Environmental microbiology [Environ Microbiol] 2016 Nov; Vol. 18 (11), pp. 3728-3741. Date of Electronic Publication: 2016 Jun 27.
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.<br /> (© 2016 Society for Applied Microbiology and John Wiley & Sons Ltd.)

Details

Language :
English
ISSN :
1462-2920
Volume :
18
Issue :
11
Database :
MEDLINE
Journal :
Environmental microbiology
Publication Type :
Academic Journal
Accession number :
26954535
Full Text :
https://doi.org/10.1111/1462-2920.13294