Biosynthetic pathways sterigmatocystin

The relationship of 13C acetate and averufin (i60)183 and very detailed 13C nuclear magnetic resonance enrichment studies of the abovementioned intermediates have recently led Steyn and co-workers184-187 to conclude187 that a biosynthetic pathway starting with polyketide (161), going through averufin (160), versicolorin A (162), and sterigmatocystin (30), eventually results in aflatoxin Bj (i). 

Figure 10.2 The sterigmatocystin and aflatoxin biosynthetic pathway. The structures of the intermediates are on the left, the names of the intermediates in the middle and the A. nidulans biosynthetic genes which encode the enzymes required to convert one intermediate to the next precursor are indicated on the right. Gene names followed by a question mark i.e., stcN) indicates that the gene is predicted, not proven, to function at this particular step in the ST pathway.

A kinetic pulse-labelling technique for the detection of transitory intermediates on the aflatoxin biosynthetic pathway has been described. It has been applied to both sterigmatocystin (85) formation in Aspergillus versicolor amd aflatoxin formation in A. parasiticus. The results are largely in accord with the accepted sequence of intermediates. However, one... 

Sterigmatocystin (15) is both a carcinogenic hepatotoxin and a biosynthetic precursor to the important mycotoxin, aflatoxin, and, as such, its biosynthesis pathway has been studied quite extensively (607-608). This is purported to begin with a single C20 polyketide unit, which is folded in only one mode to form averufin (103) and then sterigmatocystin (15) (609). The authors provided evidence to support the identity of this compound through the synthesis of a common product from both it and from a... 

The second method employed in biosynthetic studies involves the characterization of fermentation products closely related to the secondary metabolite under investigation. This method has been extensively used and has led to the implication of averufin (8), the versicolorins, and sterigmato-cystin (32) in aflatoxin biogenetic pathway. Some of the intermediates were isotopically labeled and their role in aflatoxin biosynthesis verified, e.g., sterigmatocystin by whole cell (Hsieh et al., 1973) and cell-free cultures of A. parasiticus (Singh and Hsieh, 1976). 

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