title: The fumitremorgin gene cluster of Aspergillus fumigatus: identification of a gene encoding brevianamide F synthetase.
abstract: A gene encoding a putative dimodular nonribosomal peptide synthetase (NRPS) was identified within a gene cluster of Aspergillus fumigatus, a species reported to produce fumitremorgins and other prenylated alkaloids. The gene was deleted and overexpressed in the genome reference strain Af293, and was also expressed in the naïve host Aspergillus nidulans, which lacks the equivalent gene cluster. While neither fumitremorgins nor the dipeptide brevianamide F (cyclo-L-Trp-L-Pro), an early intermediate, were detected in wild-type and deletion strains of A. fumigatus, brevianamide F accumulated in fungal cultures following increased expression of the NRPS gene in both A. fumigatus and A. nidulans. We conclude that the gene Afu8g00170, named ftmA, encodes the NRPS brevianamide synthetase. Brevianamide F is the precursor of a variety of fungal prenylated alkaloids with biological activity, including fumitremorgins A, B and C and tryprostatin B.
authors.affiliation: University of Sheffield, Department of Molecular Biology and Biotechnology, Western Bank, UK.
authors.forename: Shubha
authors.initials: S
authors.lastname: Maiya
authors.forename: Alexander
authors.initials: A
authors.lastname: Grundmann
authors.forename: Shu-Ming
authors.initials: SM
authors.lastname: Li
authors.forename: Geoffrey
authors.initials: G
authors.lastname: Turner
mesh_terms: D000470:Alkaloids / Q000096:biosynthesis; D001232:Aspergillus fumigatus / Q000201:enzymology / Q000235:genetics*; D001233:Aspergillus nidulans / Q000201:enzymology / Q000235:genetics*; D002851:Chromatography, High Pressure Liquid; D015964:Gene Expression Regulation, Bacterial / Q000235:genetics; D018014:Gene Transfer Techniques; D009682:Magnetic Resonance Spectroscopy; D010453:Peptide Synthases / Q000235:genetics*
chemical_list: D000470:Alkaloids; D010453:Peptide Synthases; C104385:non-ribosomal peptide synthase