Abstract
BackgroundAflatoxins (AFs) are potent carcinogenic compounds produced by several Aspergillus species, which pose serious threats to human health. As sugar is a preferred carbohydrate source for AF production, we examined the possibility of using sugar analogs to inhibit AF biosynthesis.ResultsWe showed that although D-glucal cannot be utilized by A. flavus as the sole carbohydrate source, it inhibited AF biosynthesis and promoted kojic acid production without affecting mycelial growth when applied to a glucose-containing medium. The inhibition occurred before the production of the first stable intermediate, norsolorinic acid, suggesting a complete inhibition of the AF biosynthetic pathway. Further studies showed that exogenous D-glucal in culture led to reduced accumulation of tricarboxylic acid (TCA) cycle intermediates and reduced glucose consumption, indicating that glycolysis is inhibited. Expression analyses revealed that D-glucal suppressed the expression of AF biosynthetic genes but promoted the expression of kojic acid biosynthetic genes.ConclusionsD-glucal as a non-metabolizable glucose analog inhibits the AF biosynthesis pathway by suppressing the expression of AF biosynthetic genes. The inhibition may occur either directly through interfering with glycolysis, or indirectly through reduced oxidative stresses from kojic acid biosynthesis.
Highlights
Aflatoxins (AFs) are potent carcinogenic compounds produced by several Aspergillus species, which pose serious threats to human health
To examine if D-glucal and D-galactal could be used as the sole carbohydrate for mycelial growth, we replaced the glucose in the medium with 20 or 40 mg/mL D-glucal or D-galactal
After incubation of A. flavus A 3.2890 spores in these media for 3 d, we observed no mycelial growth in media with D-glucal or D-galactal, while abundant mycelial growth was observed in those two controls (Figure 1)
Summary
Aflatoxins (AFs) are potent carcinogenic compounds produced by several Aspergillus species, which pose serious threats to human health. As sugar is a preferred carbohydrate source for AF production, we examined the possibility of using sugar analogs to inhibit AF biosynthesis. Aflatoxins (AFs) are highly carcinogenic secondary metabolites produced by Aspergillus species such as A. flavus and A. parasiticus after invading plants or stored grains. Contaminations of these toxins in the food chain pose serious threats to humans and animals [1,2]. Previous studies focused on understanding the molecular machinery of AF biosynthesis [3], which have shown that most genes involved in the production of AF are located in a co-regulated gene cluster that encodes two regulatory proteins (aflR and aflS) and at least 26 down-stream metabolic enzymes [4]. Sugar is the most frequently used carbohydrate for studying AF
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