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.
Publication types
-
Research Support, Non-U.S. Gov't
MeSH terms
-
Amino Acid Sequence
-
Blotting, Southern
-
Chromatography, High Pressure Liquid
-
Computational Biology
-
Gene Deletion
-
Gene Expression Regulation, Fungal
-
Genes, Fungal
-
Hydrophobic and Hydrophilic Interactions*
-
Mass Spectrometry
-
Models, Biological
-
Molecular Sequence Data
-
Oligopeptides / biosynthesis*
-
Oligopeptides / chemistry
-
Penicillium chrysogenum / enzymology*
-
Penicillium chrysogenum / genetics
-
Penicillium chrysogenum / growth & development
-
Penicillium chrysogenum / metabolism
-
Peptide Synthases / metabolism*
-
Peptides, Cyclic / biosynthesis*
-
Peptides, Cyclic / chemistry
-
Secondary Metabolism
Substances
-
Oligopeptides
-
Peptides, Cyclic
-
Peptide Synthases
-
non-ribosomal peptide synthase
Grants and funding
HA and MR were supported by STW (Stichting Technische Wetenschappen) in the framework of the Genbiotics Perspectief Programme. HA was also supported by Higher education commission Pakistan (HEC). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.