THE ASPERGILLUS-PARASITICUS POLYKETIDE SYNTHASE GENE PKSA, A HOMOLOG OF ASPERGILLUS-NIDULANS WA, IS REQUIRED FOR AFLATOXIN B-1 BIOSYNTHESIS

Aflatoxins comprise a group of polyketide-derived carcinogenic mycotox ins produced by Aspergillus parasiticus and Aspergillus flavus. By tra nsformation with a disruption construct, pXX, we disrupted the aflatox in pathway in A. parasiticus SRRC 2043, resulting in the inability of this strain to produce aflatoxin intermediates as well as a major yell ow pigment in the transformants. The disruption was attributed to a si ngle-crossover, homologous integration event between pXX and the recip ient A. parasiticus genome at a specific locus, designated pksA. Seque nce analysis suggest that pksA is a homolog of the Aspergillus nidulan s wA gene, a polyketide synthase gene involved in conidial wall pigmen t biosynthesis. The conserved beta-ketoacyl synthase, acyltransferase and acyl carrier-protein domains were present in the deduced amino aci d sequence of the pksA product. No beta-ketoacyl reductase and enoyl r eductase domains were found, suggesting that pksA does not encode cata lytic activities for processing beta-carbon similar to those required for long chain fatty acid synthesis. The pksA gene is located in the a flatoxin pathway gene cluster and is linked to the nor-1 gene; an afla toxin pathway gene required for converting norsolorinic acid to averan tin. These two genes are divergently transcribed from a 1.5 kb interge nic region. We propose that pksA is a polyketide synthase gene require d for the early steps of aflatoxin biosynthesis.