adhA in Aspergillus parasiticus is involved in conversion of 5'-hydroxyaverantin to averufin

Appl Environ Microbiol. 2000 Nov;66(11):4715-9. doi: 10.1128/AEM.66.11.4715-4719.2000.

Abstract

Two routes for the conversion of 5'-hydroxyaverantin (HAVN) to averufin (AVF) in the synthesis of aflatoxin have been proposed. One involves the dehydration of HAVN to the lactone averufanin (AVNN), which is then oxidized to AVF. Another requires dehydrogenation of HAVN to 5'-ketoaverantin, the open-chain form of AVF, which then cyclizes spontaneously to AVF. We isolated a gene, adhA, from the aflatoxin gene cluster of Aspergillus parasiticus SU-1. The deduced ADHA amino acid sequence contained two conserved motifs found in short-chain alcohol dehydrogenases-a glycine-rich loop (GXXXGXG) that is necessary for interaction with NAD(+)-NADP(+), and the motif YXXXK, which is found at the active site. A. parasiticus SU-1, which produces aflatoxins, has two copies of adhA (adhA1), whereas A. parasiticus SRRC 2043, a strain that accumulates O-methylsterigmatocystin (OMST), has only one copy. Disruption of adhA in SRRC 2043 resulted in a strain that accumulates predominantly HAVN. This result suggests that ADHA is involved in the dehydrogenation of HAVN to AVF. Those adhA disruptants that still made small amounts of OMST also accumulated other metabolites, including AVNN, after prolonged culture.

MeSH terms

  • Alcohol Dehydrogenase / genetics
  • Alcohol Dehydrogenase / metabolism*
  • Alcohol Oxidoreductases / genetics
  • Alcohol Oxidoreductases / metabolism*
  • Anthraquinones / metabolism*
  • Aspergillus / enzymology*
  • Aspergillus / genetics
  • Aspergillus / growth & development
  • Gene Deletion
  • Genes, Fungal
  • Molecular Sequence Data
  • Sequence Analysis, DNA

Substances

  • Anthraquinones
  • 5'-hydroxyaverantin
  • averufin
  • Alcohol Oxidoreductases
  • Alcohol Dehydrogenase

Associated data

  • GENBANK/U76621