Biosynthesis of aflatoxins. Incorporation of [2-2H3]acetate into aflatoxin B1 by Aspergillus flavus

Abstract

The observation of an NIH shift on incorporation of [2H3]acetate into aflatoxin B, in cultures of Aspergillus flaws provides evidence for the timing of deoxygenation and hydroxylation steps which are an essential part of the biosynthetic pathway.

Aziridine Natural Products – Discovery, Biological Activity and Biosynthesis

“…This result is consistent with the involvement of an 'NIH shift' mechanism for hydroxylation of aromatic rings (Figure 11.16) [155]. This was first observed in the oxidation of aromatic amino acids, although at least one other example has been found for its involvement in polyketide biosynthesis, during the construction of aflatoxin B1 [156].…”

Absence of the aflatoxin biosynthesis gene, norA, allows accumulation of deoxyaflatoxin B1 in Aspergillus flavus cultures

“…The oxidative ring cleavage and rearrangement necessary for the formation of the coumarin ring system in AFB 1 must be consistent with the following observations: (a) NADPH is utilized in the conversion (Singh & Hsieh, 1976); (b) an 'NIH hydride shift' occurs so that the C-11 hydrogen is retained (Simpson et al, 1983); (c) an oxygen atom and carbon-11 in the A-ring of OMST are lost as carbon dioxide (Chatterjee & Townsend, 1994); and (d) an oxygen atom incorporated into the B-ring (Scheme 1) is retained (Watanabe & Townsend, 1996).…”

Oxidative rearrangements during fungal biosynthesis

“…Since this carbon derives from C-1 of acetate there must have been a 1,2-deuterium migration during biosynthesis and this was rationalised as being due to an NIH-shi (Scheme 11). 38 This work also implicated 11-hydroxy-O-methylsterigmatocystin (HOMST) 54b as a pathway intermediate, but at this stage this could not be proven.…”