|Wheeler, Michael - Mike|
Submitted to: American Society for Microbiology
Publication Type: Abstract Only
Publication Acceptance Date: 4/15/1999
Publication Date: N/A
Technical Abstract: Aspergillus fumigatus, a filamentous fungus producing bluish-green conidia, is an important opportunistic pathogen among immunocompromised patients. Conidial pigment biosynthesis has previously been shown to influence A. fumigatus virulence greatly in a murine model. Six genes, forming a gene cluster spanning 19kb, were identified and found to involve in the complex conidial pigment biosynthesis in A. fumigatus. Northern blot analysis showed that these six genes were developmentally regulated, being expressed during conidiation. Gene alb1, arp1, and arp2 encoded putative proteins that exhibited respective similarities with polyketide synthase, scytalone dehydratase, and 1,3,8-trihydroxynaphthalene reductase which are involved in DHN-melanin biosynthesis. Sequence database search revealed that abr1 possessed multicopper oxidase signatures and abr2 shared homology with the Aspergillus nidulans yA gene encoding a laccase. Function of the aryg1 gene remains unknown. Involvement of these genes in conidial pigment biosynthesis was confirmed by disrupting each gene individually which resulted in conidial color alteration. Presence of a DHN-melanin pathway in A. fumigatus was supported by detection o the accumulation of scytalone in the arp1 disruptant and flaviolin in the arp2 disruptants. Scytalone and flaviolin are hallmark intermediates and branch products of a DHN- melanin pathway reported in fungi. The sequence similarity suggested that alb1, arp2, and arp1 catalyze the first three steps of this pigment biosynthetic pathway. Results of double gene disruptions suggested the probable order of abr1, abr2, and ayg1 in the pathway.