Influence of tricarboxylic acid cycle intermediates and related metabolites on the biosynthesis of aflatoxin by resting cells of Aspergillus flavus

Abstract

Resting cells of Aspergillus flavus synthesized aflatoxin from acetate as the sole carbon source after 36 h of incubation. Addition of pyruvate (5.5 mg/ml) as cosubstrate to [1-'4C]acetate and unlabeled acetate considerably reduced toxin production but increased the radioactivity on the tricarboxylic acid intermediates. This suggests that high tricarboxylic acid activity drastically affected toxin synthesis. '[he carcinogenic property of aflatoxin has stimulated many scientists to study in detail the mode of action, metabolism, and biosynthesis of this toxin. Adye and Mateles (1) have shown the incorporation of labeled carbon from phenylalanine, tyrosine, acetate, and methionine into the toxin molecule. Donkersloot et al. (8), however, excluded the possible involvement of phenylalanine and shikimic acid as biogenetic precursors. Biollaz and co-workers (3) advanced the hypothesis that a polyhydroxy naphthacene and endoperoxy anthraquinone were the intermediates derived from acetate in aflatoxin synthesis. Subsequently, Donkersloot et al. (9) obtained a mutant of Aspergillus parasiticus, with an impaired pathway of aflatoxin biosynthesis, that accumulated averufin, which was shown later by Lin and co-workers to be incorporated into aflatoxin B1 (13). Basappa et al. (2) have shown that acetate is a good precursor for aflatoxin and that kojic acid is not an intermediate in its synthesis. This communication presents some evidence t.o show that the biosynthesis of aflatoxin from acetate follows a route not involving the tricarboxylic acid cycle. MATERIALS AND METHODS All the solvents and chemicals used were of analytical grade. Sodium [1-'4C]acetate was supplied by

Regulation ofaflRand Its Product, AflR, Associated with Aflatoxin Biosynthesis

“…Although intensive studies of the factors affecting aflatoxin formation have been carried out in the last three decades, the mechanism that regulates aflatoxin formation remains poorly understood. The availability of readily utilizable carbohydrates, levels of certain intermediates in primary metabolism, and the cytoplasmic anabolic reduction charge ratio of NADPH to NADP are all important (24,29). More recently, most of the genes involved in the biosynthesis of aflatoxin were identified, and evidence for a complex interaction between environmental and nutritional factors and the genetic characteristics of the fungi was obtained (21).…”

Stimulation of aflatoxin B1 and T-2 toxin production by sorbic acid

“…The tricarboxylic acid cycle plays a central role in catabolic and anabolic processes in fungi. It was pointed out that tricarboxylic acid intermediates inhibit aflatoxin production (2,20). On the other hand, Gupta et al (8) demonstrated that increased aflatoxin production was correlated with decreased activity of the tricarboxylic acid cycle.…”

Advanced mycotoxin control and decontamination techniques in view of an increased aflatoxin risk in Europe due to climate change

“…Simple sugars and acetate stimulate ( Shantha and Murthy, 1981 ), and intermediates of the tricarboxylic acid cycle inhibit the formation of AF ( Buchanan and Ayres, 1977 ; Shantha and Murthy, 1981 ). Although, at the same time, carbon sources do not regulate specifically the genes in the AF biosynthesis pathway.…”