title: Co-ordination between BrlA regulation and secretion of the oxidoreductase FmqD directs selective accumulation of fumiquinazoline C to conidial tissues in Aspergillus fumigatus.
abstract: Aerial spores, crucial for propagation and dispersal of the Kingdom Fungi, are commonly the initial inoculum of pathogenic fungi. Natural products (secondary metabolites) have been correlated with fungal spore development and enhanced virulence in the human pathogen Aspergillus fumigatus but mechanisms for metabolite deposition in the spore are unknown. Metabolomic profiling of A. fumigatus deletion mutants of fumiquinazoline (Fq) cluster genes reveal that the first two products of the Fq cluster, FqF and FqA, are produced to comparable levels in all fungal tissues but the final enzymatically derived product, FqC, predominantly accumulates in the fungal spore. Loss of the sporulation-specific transcription factor, BrlA, yields a strain unable to produce FqA or FqC. Fluorescence microscopy showed FmqD, the oxidoreductase required to generate FqC, was secreted via the Golgi apparatus to the cell wall in an actin-dependent manner. In contrast, all other members of the Fq pathway including the putative transporter, FmqE - which had no effect on Fq biosynthesis - were internal to the hyphae. The co-ordination of BrlA-mediated tissue specificity with FmqD secretion to the cell wall presents a previously undescribed mechanism to direct localization of specific secondary metabolites to spores of the differentiating fungus.
authors.affiliation: Department of Medical Microbiology and Immunology, University of Wisconsin-Madison, Madison, WI, USA.
authors.forename: Fang Yun
authors.initials: FY
authors.lastname: Lim
authors.forename: Brian
authors.initials: B
authors.lastname: Ames
authors.forename: Christopher T
authors.initials: CT
authors.lastname: Walsh
authors.forename: Nancy P
authors.initials: NP
authors.lastname: Keller
mesh_terms: D001232:Aspergillus fumigatus / Q000235:genetics*; D005656:Fungal Proteins / Q000235:genetics*; D015966:Gene Expression Regulation, Fungal; D010088:Oxidoreductases / Q000096:biosynthesis* / Q000378:metabolism; D011799:Quinazolines / Q000378:metabolism; D013172:Spores, Fungal / Q000235:genetics / Q000254:growth & development* / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics*; D014364:Tryptophan / Q000031:analogs & derivatives / Q000378:metabolism
chemical_list: C000597190:BrlA protein, Aspergillus fumigatus; D005656:Fungal Proteins; D011799:Quinazolines; D014157:Transcription Factors; C419468:fumiquinazoline A; C454622:fumiquinazoline C; C504706:fumiquinazoline F; D014364:Tryptophan; D010088:Oxidoreductases