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Title: CONIDIAL PIGMENT BIOSYNTHESIS IN ASPERGILLUS FUMIGATUS: USE OF MUTANT STRAINS AND TRICYCLAZOLE TO STUDY THE METABOLISM OF SCYTALONE AND 1,3,8-TRIHYDROXYNAPHTHALENE

Author
item Wheeler, Michael - Mike
item TSAI, H - NIH
item KWON-CHUNG, K - NIH

Submitted to: American Society for Microbiology
Publication Type: Abstract Only
Publication Acceptance Date: 5/17/1998
Publication Date: N/A
Citation: N/A

Interpretive Summary:

Technical Abstract: Previously we showed that the bluish-green conidial pigment of A. fumigatus is made via pentaketide biosynthesis. Also, we showed that tricyclazole blocked synthesis of the pigment by inhibiting the enzymic reduction of 1,3,6,8-tetrahydroxynaphthalene (1,3,6,8-THN) to scytalone. In the present study we grew three strains of A. fumigatus on asparagine-sucrose-agar medium (ASA) to determine how they metabolize scytalone in the presence and absence of tricyclazole. We used a wild type strain (B-5233), an albino conidial color mutant (B-5233/RGD12-8) that is deficient for the polyketide synthase, and a reddish brown color mutant (B-5233/RGD10-1) that is deficient for 1,3,6,8-THN reductase. The fungi were grown on ASA or on ASA amended with 1 mM scytalone or 1 mM scytalone and 30 ug/ml tricyclazole. In cultures without tricyclazole, all three strains dehydrated scytalone to 1,3,8-THN which was then mostly metabolized to a bluish-green to gray pigment associated with hyphae on the reverse side of the fungal colony. Some 1,3,8-THN was autooxidized to 2-hydroxy-juglone (2-HJ) that accumulated in the agar medium. Tricyclazole prevented synthesis of the bluish-green pigment and caused accumulation of 2-HJ by preventing reduction of 1,3,8-THN. These studies indicate that tricyclazole inhibits the enzymic reduction of 1,3,8-THN to a downstream pigment precursor. This observation is important because it suggests that 1,3,6,8-THN and 1,3,8-THN are reduced by different reductases.