Abstract
Biosynthesis of the toxic and carcinogenic aflatoxins (AFs) requires the activity of more than 27 enzymes. The roles in biosynthesis of newly described enzymes are discussed in this review. We suggest that HypC catalyzes the oxidation of norsolorinic acid anthrone; AvfA (AflI), the ring-closure step in formation of hydroxyversicolorone; HypB, the second oxidation step in conversion of O-methylsterigmatocystin to AF; and HypE and NorA (AflE), the final two steps in AFB1 formation. HypD, an integral membrane protein, affects fungal development and lowers AF production while AflJ (AflS), has a partial methyltransferase domain that may be important in its function as a transcriptional co-activator.
Highlights
The aflatoxins (AFs) are the most studied of all of the fungal toxins
Only 11 of the 29 enzymes and regulatory factors involved in the biosynthesis have been isolated and their activity characterized by kinetic studies, and, of these, only some have been assigned to specific catalytic steps in the biosynthesis pathway
Gene Clusters and Aflatoxin Biosynthesis. It is fortunate for understanding the function of the genes and proteins involved in AF biosynthesis in A. flavus and A. parasiticus that all of the genes are maintained in a 75 kbp gene cluster [23,24]
Summary
The aflatoxins (AFs) are the most studied of all of the fungal toxins (for recent reviews, see references [1,2,3,4,5,6,7,8,9,10]). The characterized genes encode enzymes involved in biosynthetic steps starting from the precursors, malonyl and acetylCoA Since their discovery in 1960, the main biosynthetic steps have been identified and detailed reviews of the chemistry and biosynthesis of AF formation are available [4,16,19,20,21,22]. Only 11 of the 29 enzymes and regulatory factors involved in the biosynthesis have been isolated and their activity characterized by kinetic studies, and, of these, only some have been assigned to specific catalytic steps in the biosynthesis pathway Because of this inadequate knowledge of protein function, some of this review’s conclusions on the role of the enzymes will be, of necessity, speculative. Because the literature regarding AF biosynthesis is so extensive, placing the newly discovered hypothetical enzymes and some of the older, as yet, uncharacterized enzymes into the biosynthetic puzzle should help to better understand the complexity of the biosynthesis and the logic behind some of these steps
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