A Requirement for 2-Methylcitrate Synthase for Sterigmatocystin Biosynthesis and Sexual Development in Aspergillus Nidulans

Yongqiang Zhang, Nancy Keller


Sterigmatocystin (ST) is a carcinogenic polyketide produced by several Aspergillus species including A. nidulans. We have complemented a ST mutant with the 2-methylcitrate synthase gene (mscA). 2-Methyl citrate synthase catalyzes the conversion of propionyl CoA to 2-Methyl citrate, which is a key step in 2-Methyl citrate cycle enabling the fungus to use propionate as a carbon source. Along with a decrease in ST production and loss of the ability to utilize propionate as the sole carbon source, the mcsA deletion and mutation strains are impaired in their sexual development. Addition of pyruvate is unable to restore ST production, thus ruling out the possibility that pyruvate generated from 2-methylcitrate cycle is required for ST production. Blocks at mscA result in a build up of propionyl CoA, suggesting that the accumulating propionyl CoA in the mcsA mutant strains interfere with the function of certain biosynthetic enzyme(s) involved in ST production. To examine this hypothesis, we are currently disrupting the putative propionyl CoA synthase encoding gene pcsA, which is required for the conversion of propionate to propionyl CoA.

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American Society for Microbiology General Meeting
    • ASM 102nd (2002)