1. A Non-Canonical NRPS Is Involved in the Synthesis of Fungisporin and Related Hydrophobic Cyclic Tetrapeptides in Penicillium chrysogenum
- Author
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Roel A. L. Bovenberg, Noël Nicolaas Maria Elisabeth Van Peij, Olaf Leonardus Schouten, Peter P. Lankhorst, Marek J. Noga, Thomas Hankemeier, Rob van der Hoeven, Hazrat Ali, Rob J. Vreeken, Arnold J. M. Driessen, Marco Ries, Molecular Microbiology, and Groningen Biomolecular Sciences and Biotechnology
- Subjects
Applied Microbiology ,POLYKETIDE ,Secondary Metabolism ,Plant Science ,Penicillium chrysogenum ,Biochemistry ,Mass Spectrometry ,Protein sequencing ,Gene Expression Regulation, Fungal ,Peptide Synthases ,Fungal Biochemistry ,Peptide sequence ,SPECIFICITY ,Chromatography, High Pressure Liquid ,chemistry.chemical_classification ,Oligopeptide ,Multidisciplinary ,Plant Biochemistry ,Fungal genetics ,NONRIBOSOMAL PEPTIDE SYNTHETASES ,Blotting, Southern ,Medicine ,Hydrophobic and Hydrophilic Interactions ,Oligopeptides ,YERSINIA-PESTIS ,Research Article ,Biotechnology ,EXPRESSION ,Science ,Protein domain ,Genes, Fungal ,Molecular Sequence Data ,BIOGENESIS ,Mycology ,Biology ,Models, Biological ,Peptides, Cyclic ,Microbiology ,Polyketide ,Industrial Microbiology ,Nonribosomal peptide ,BIOSYNTHESIS ,Amino Acid Sequence ,PURIFICATION ,Organisms ,Fungi ,Computational Biology ,Biology and Life Sciences ,biology.organism_classification ,Metabolism ,chemistry ,Small Molecules ,ADENYLATION DOMAIN ,ASSEMBLY-LINE ENZYMOLOGY ,Gene Deletion - Abstract
The filamentous fungus Penicillium chrysogenum harbors an astonishing variety of nonribosomal peptide synthetase genes, which encode proteins known to produce complex bioactive metabolites from simple building blocks. Here we report a novel non-canonical tetra-modular nonribosomal peptide synthetase (NRPS) with microheterogenicity of all involved adenylation domains towards their respective substrates. By deleting the putative gene in combination with comparative metabolite profiling various unique cyclic and derived linear tetrapeptides were identified which were associated with this NRPS, including fungisporin. In combination with substrate predictions for each module, we propose a mechanism for a 'trans-acting' adenylation domain.
- Published
- 2014
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