title: The Aspergillus parasiticus polyketide synthase gene pksA, a homolog of Aspergillus nidulans wA, is required for aflatoxin B1 biosynthesis.
abstract: Aflatoxins comprise a group of polyketide-derived carcinogenic mycotoxins produced by Aspergillus parasiticus and Aspergillus flavus. By transformation with a disruption construct, pXX, we disrupted the aflatoxin pathway in A. parasiticus SRRC 2043, resulting in the inability of this strain to produce aflatoxin intermediates as well as a major yellow pigment in the transformants. The disruption was attributed to a single-crossover, homologous integration event between pXX and the recipient A. parasiticus genome at a specific locus, designated pksA. Sequence analysis suggest that pksA is a homolog of the Aspergillus nidulans wA gene, a polyketide synthase gene involved in conidial wall pigment biosynthesis. The conserved beta-ketoacyl synthase, acyltransferase and acyl carrier-protein domains were present in the deduced amino acid sequence of the pksA product. No beta-ketoacyl reductase and enoyl reductase domains were found, suggesting that pksA does not encode catalytic activities for processing beta-carbon similar to those required for long chain fatty acid synthesis. The pksA gene is located in the aflatoxin pathway gene cluster and is linked to the nor-1 gene, an aflatoxin pathway gene required for converting norsolorinic acid to averantin. These two genes are divergently transcribed from a 1.5 kb intergenic region. We propose that pksA is a polyketide synthase gene required for the early steps of aflatoxin biosynthesis.
authors.affiliation: Department of Cell and Molecular Biology, Tulane University, New Orleans, Louisiana 70118, USA.
authors.forename: P K
authors.initials: PK
authors.lastname: Chang
authors.forename: J W
authors.initials: JW
authors.lastname: Cary
authors.forename: J
authors.initials: J
authors.lastname: Yu
authors.forename: D
authors.initials: D
authors.lastname: Bhatnagar
authors.forename: T E
authors.initials: TE
authors.lastname: Cleveland
mesh_terms: D016604:Aflatoxin B1 / Q000096:biosynthesis*; D000595:Amino Acid Sequence; D001230:Aspergillus / Q000201:enzymology* / Q000235:genetics*; D001233:Aspergillus nidulans / Q000201:enzymology / Q000235:genetics; D001483:Base Sequence; D008969:Molecular Sequence Data; D009097:Multienzyme Complexes / Q000737:chemistry / Q000235:genetics*; D010860:Pigments, Biological / Q000378:metabolism; D017386:Sequence Homology, Amino Acid
chemical_list: D009097:Multienzyme Complexes; D010860:Pigments, Biological; D016604:Aflatoxin B1