AI Article Synopsis

  • The genome sequence of Aspergillus fumigatus contains a unique hybrid gene (PKS/NRPS) involved in secondary metabolism, which is part of a five-gene cluster.
  • Evidence shows that this gene is crucial for the production of pseurotin A, a compound known for its unusual structure and biological properties, including inhibition of chitin synthase and promotion of nerve cell growth.
  • Manipulating the expression of the psoA gene directly affects the levels of pseurotin A, confirming its essential role in its biosynthesis.

Article 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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http://dx.doi.org/10.1002/cbic.200700202DOI Listing

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