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A non-canonical NRPS is involved in the synthesis of fungisporin and related hydrophobic cyclic tetrapeptides in Penicillium chrysogenum.

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.

SUBMITTER: Ali H

PROVIDER: S-EPMC4041764 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature

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A non-canonical NRPS is involved in the synthesis of fungisporin and related hydrophobic cyclic tetrapeptides in Penicillium chrysogenum.

Ali Hazrat H Ries Marco I MI Lankhorst Peter P PP van der Hoeven Rob A M RA Schouten Olaf L OL Noga Marek M Hankemeier Thomas T van Peij Noël N M E NN Bovenberg Roel A L RA Vreeken Rob J RJ Driessen Arnold J M AJ

PloS one 20140602 6

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 uni ...[more]

PMID: 24887561

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