Biosynthesis of aflatoxin. Conversion of norsolorinic acid and other hypothetical intermediates into aflatoxin B1

Abstract

A, the RSA should be 0.9 if labeling is the same as that expected from averufin (Lin et al., 1973). In our experiments the quite low RSA for aflatoxin made from acetate (0.007) compared to the relatively high RSA (0.475) for aflatoxin made from the labeled versicolorin A pigment offers additional strong evidence that this pigment is incorporated essentially intact and is not broken down into acetate units before incorporation into aflatoxin . report 45-58% conversion of sterigmatocystin to aflatoxin and conclude that sterigmatocystin or a closely related metabolite is an intermediate in the biosynthesis of aflatoxins. The 46% conversion of versicolorin A to aflatoxin found in our experiments suggests that this pigment is as efficiently converted to aflatoxin as is sterigmatocystin and offers experimental proof to the theory hypothesized by Heathcote et al. (1973) in which they propose versicolorin A as a precursor to aflatoxin .

Aflatoxins and Anthraquinones from Diploids of Aspergillus parasiticus

“…parasiticus, the yellow-pigmented, mutant haploid strain wkz-1 ver-1 can be considered an ' aflatoxin idiotroph' since it is completely blocked in aflatoxin production; however, when supplied with sterigmatocystin, an aflatoxin precursor occurring later in the pathway, aflatoxin production occurs (Singh & Hsieh, 1977). The red-pigmented, haploid mutant strain br-1 nor-1 produces norsolorinic acid, a known aflatoxin precursor (Hsieh et al, 1976), but is not completely blocked in aflatoxin production. Perhaps by analogy to the terminology applied to auxotrophic genes, it can be termed a 'leaky idiotroph'.…”

“…To date, there are five known intermediates in aflatoxin biosynthesis : sterigmatocystin, versiconal hemiacetal acetate, averufin, norsolorinic acid and versicolorin A Singh & Hsieh, 1977;Hsieh et al, 1976). The last three are all anthraquinone pigments accumulated by mutants impaired in aflatoxin biosynthesis.…”

Isolation and Characterization of the Versicolorin B Synthase Gene from Aspergillus parasiticus

“…This primer is homologated by successive malonyl condensations to give, after intramolecular aldol condensation, cyclization, and oxidation, norsolorinic acid (3) (19 -21). Simple redox changes in the hexanoyl side chain yield the internal ketal averufin (4) (22)(23)(24). Oxidation at C-2Ј of 4 induces migration of the anthraquinone nucleus from C-1Ј to C-2Ј to afford hydroxyversicolorone (5) containing the first furan ring (25,26).…”

Characterization of the polyketide synthase gene (pksL1) required for aflatoxin biosynthesis in Aspergillus parasiticus

“…A typical AF, AFB 1 for example, is produced by the following generally accepted pathway: acetate building blocks (also hexanoate)3anthrone-derivative polyketide3norsolorinic acid (NA)3averanfin3averufin3hydroxyversicolorine3versiconal hemiacetal acetate3versicolorin B3versicolorin A3sterig-matocystin3o-methylsterigmatocystin3AFB 1 (13,15,27,58). NA is polyketide derived and represents the first stable intermediate in AF biosynthesis (34,37). An unstable anthronederivative polyketide has been proposed as a hypothetical intermediate formed prior to NA, but this theoretical polyketide has not been isolated, presumably because it is rapidly oxidized to NA (27).…”