Identification of a Hybrid PKS/NRPS Required for Pseurotin A Biosynthesis in the Human Pathogen Aspergillus fumigatus
- 13 September 2007
- journal article
- research article
- Published by Wiley in ChemBioChem
- Vol. 8 (14), 1736-1743
- https://doi.org/10.1002/cbic.200700202
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 γ-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.Keywords
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