1. Academic Validation
  2. Identification of a hybrid PKS/NRPS required for pseurotin A biosynthesis in the human pathogen Aspergillus fumigatus

Identification of a hybrid PKS/NRPS required for pseurotin A biosynthesis in the human pathogen Aspergillus fumigatus

  • Chembiochem. 2007 Sep 24;8(14):1736-43. doi: 10.1002/cbic.200700202.
Shubha Maiya 1 Alexander Grundmann Xiang Li Shu-Ming Li Geoffrey Turner
Affiliations

Affiliation

  • 1 University of Sheffield, Department of Molecular Biology and Biotechnology, S10 2TN, Sheffield, UK.
Abstract

The genome sequence of Aspergillus fumigatus revealed the presence of a single hybrid polyketide synthase-non-ribosomal peptide synthetase (PKS/NRPS) gene that is present within a cluster of five genes suggestive of its involvement in secondary metabolism. Here, we present evidence that it is required for the biosynthesis of pseurotin A, a compound with an unusual heterospirocyclic gamma-lactam structure. We have confirmed that the genome reference strain A. fumigatus Af293 produces pseurotin A, a compound previously reported to be a competitive inhibitor of chitin synthase and an inducer of nerve-cell proliferation. Deletion or overexpression of the PKS/NRPS gene psoA in A. fumigatus leads to the absence or accumulation of pseurotin A, respectively; this indicates that this gene is essential for the biosynthesis of pseurotin A. It is likely that the first product of psoA is converted to pseurotin A by the products of other genes in this cluster.

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