The non-metabolizable glucose analog D-glucal inhibits aflatoxin biosynthesis and promotes kojic acid production in Aspergillus flavus

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.

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“…In this study, the use of S. roseolus simultaneously reduced the AFB 1 and KA concentrations. On the contrary, other authors observed a reduction in the AFB 1 concentration with an increase in the KA concentration by using D-glucal, C18:3 fractions, and dioctatin-A [ 25 , 26 , 27 ]. These results suggest the production of A. flavus secondary metabolites depends on the used agent.…”

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“…S1 B , S2 B , S3 B ). Because the growth and aflatoxin biosynthesis could be affected by different carbon sources in Aspergillus ( 19 , 22 , 61 – 63 ), we next sought to assess whether aflatoxin biosynthesis would be affected by the improved media using TLC analysis. As shown in Fig.…”

Aflatoxin Biosynthesis and Genetic Regulation: A Review

“…Simple sugars (e.g., sucrose, glucose, fructose, sorbitol) used as carbon sources have been correlated with higher levels of AF production in A. flavus, A. parasiticus and A. nidulans [29,[96][97][98]. However, the use of D-glucal (a glucose-derivative not metabolized by fungi), used as the main source of sugar in the culture medium, inhibited AFB1 production [99].…”