Stereochemistry During Aflatoxin Biosynthesis: Conversion of Norsolorinic Acid to Averufin

Appl Environ Microbiol. 1993 Aug;59(8):2486-92.

Abstract

A reaction sequence, norsolorinic acid (NA)-->averantin (AVN)-->5'-hydroxyaverantin (HAVN)-->averufin (AVR), is the early part of a biosynthetic pathway for aflatoxins. In this study, we determined the stereochemical relationship among these metabolites by using chiral high-performance liquid chromatography. In cell-free experiments using the cytosol fraction of Aspergillus parasiticus NIAH-26, (1'S)-AVN was exclusively produced from NA in the presence of NADPH. Also, only (1'S)-AVN, and not (1'R)-AVN, served as a substrate for the reverse reaction from AVN to NA. When the microsome fraction of NIAH-26 was incubated with (1'S)-AVN in the presence of NADPH, two HAVN diastereomers and one AVR enantiomer were formed, whereas these substances were never produced from (1'R)-AVN. Moreover, (1'S,5'R)-AVR was exclusively formed from both HAVN diastereomers by the cytosol fraction in the presence of NAD. The feeding experiments using this mutant showed that aflatoxins were produced from (1'S,5'R)-AVR but not from (1'R,5'S)-AVR. These results indicate that the enzymes involved in this pathway show strict stereospecificity to their substrates and that the configuration of (1'S,5'R)-AVR leading to the formation of aflatoxins is due to the stereospecificity of NA dehydrogenase which catalyzes the reaction between (1'S)-AVN and NA.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aflatoxins / biosynthesis*
  • Aflatoxins / chemistry
  • Anthraquinones / chemistry
  • Anthraquinones / metabolism
  • Aspergillus / metabolism
  • Cytosol / metabolism
  • Stereoisomerism

Substances

  • Aflatoxins
  • Anthraquinones
  • averufin
  • norsolorinic acid