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Identification of a Hybrid PKS/NRPS Required for Pseurotin A Biosynthesis in the Human Pathogen Aspergillus fumigatus
Author(s) -
Maiya Shubha,
Grundmann Alexander,
Li Xiang,
Li ShuMing,
Turner Geoffrey
Publication year - 2007
Publication title -
chembiochem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.05
H-Index - 126
eISSN - 1439-7633
pISSN - 1439-4227
DOI - 10.1002/cbic.200700202
Subject(s) - aspergillus fumigatus , polyketide synthase , gene cluster , biology , biosynthesis , gene , polyketide , atp synthase , secondary metabolism , biochemistry , genome , genetics , microbiology and biotechnology
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.