SOME NATURAL AND SYNTHETIC COMPOUNDS INHIBITING THE BIOSYNTHESIS OF AFLATOXIN B1 AND MELANIN IN Aspergillus flavus

Abstract

A b s t r a c tThe control of the mycotoxin contamination of agricultural products represents a serious problem of the global food and feed industry. Aflatoxin B1 (AFB1) is one of the most dangerous mycotoxins due to its hepatotoxicity, carcinogenicity, and temperature resistance. Thus, the search for substances able to block its biosynthesis and, therefore, to prevent the toxin accumulation in food and feed is still relevant. This paper is devoted to the study of the ability of some natural and synthesized compounds to block the biosynthesis of AFB1 and/or melanin (both are secondary metabolites, which have common intermediates and common initial stages of the polyketide biosynthetic pathway) in toxigenic Aspergillus flavus. The studied compounds included lovastatin, and several commercial compounds: (aminoethyl)thiophosphonic acid, (aminomethyl)thiophosphonic acid, alafosfalin, (1-aminoethyl)phosphonic acid, and N-hydroxyputrescine. A mutant Aspergillus terreus strain 45-50 obtained earlier from the A. terreus ATCC 20542 was used as the lovastatin producer. N-hydroxyputrescine and some phosphoanalogues of amino acids were assessed by their influence on the pigmentation of fungal colonies grown on solid medium and on the specific AFB1 content in cultural broth determined after the cultivation of a fungus on liquid nutrition medium. According to the obtained results, the studied compounds were divided into three groups. To reveal changes in the colony morphology, toxigenic A. flavus strain AF11 was cultivated on agarized medium. Concentrations of tested compounds in the medium varied from 0.0001 to 0.1 % depending on their activity. To determine the effect of tested compounds on the AFB1 production, AF11 was cultivated for 170 h in a liquid Payne-Hagler medium. Solutions of the tested compounds were added to the medium up to the final concentration of 0.001-0.1 % (commercial compounds) or 0.0001 to 0.001 % (lovastatin). The efficiency of the AFB1 biosynthesis stimulation/inhibition was assessed by the comparison of its content in the cultural broth in the experimental and control (medium without additions) variants. In addition, the effect of lovastatin on the AFB1 accumulation in wheat grain contaminated with A. flavus AF11 was assessed. The performed screening allowed us to divide the studied compounds into three groups. The supplement of the nutrition medium with (aminoethyl)thiophosphonic acid, (aminomethyl)thiophosphonic acid, and alafosfalin caused a significant decrease in the AFB1 production, but did not influenced on the colony pigmentation. N-hydroxyputrescine and (1-aminoethyl)phosphonic acid were able to partially or completely block the melanin biosynthesis with the simultaneous increase in the AFB1 production. Lovastatin completely blocked both AFB1 and melanin production even at low concentrations (0.0005 %). Therefore, compounds from the first and second groups inhibit the AFB1 or melanin biosynthesis, respectively, via the blocking of stages located after the point of divergence of the correspon...

Glyphosate inhibits melanization and increases susceptibility to infection in insects

“…We found that other phosphate-containing compounds inhibited melanization in a similar manner including phosphoserine, phosphoacetic acid, pyrophosphate, and phosphoric acid. This is in line with literature reports that other aminophosphonic acids inhibit fungal eumelanin in the human pathogen Aspergilius flavus [ 118 ]. Incidentally, this class of compounds is patented for use in human cosmetics and is marketed as solutions to inhibit melanogenesis in the skin [ 119 , 120 ].…”

Effect of Various Compounds Blocking the Colony Pigmentation on the Aflatoxin B1 Production by Aspergillus flavus

“…An increased AFB1 production was also observed in the case of thymol and 3-HBA. Thus, the effect of these three compounds was similar to that observed earlier for N -hydroxyputrescine and (1-aminoethyl)phosphonic acid [24]. …”

“…We also revealed several such compounds in our previous studies [14,24]. This effect can be explained by the common initial biosynthetic stages of both metabolites first hypothesized by Brown and Salvo [13].…”

“…Among the planned theoretical tasks, we can mention the determination of the exact point of compactin action in the polyketide biosynthetic pathway using known intermediates and the study of the compactin effect on other mycotoxins of the polyketide origin, such as zearalenone. The authors also plan to continue the study of other statins for their potential as AFB1 inhibitors and have already obtained promising results for lovastatin [24]. Note that, according to the obtained data, compactin is able to inhibit the toxinogenesis at very low concentrations.…”

Glyphosate Inhibits Melanization and Increases Susceptibility to Infection in Insects

“…We found that other phosphate-containing compounds inhibited melanization in a similar manner including phosphoserine, phosphoacetic acid, pyrophosphate and phosphoric acid. This is in line with literature reports that other aminophosphonic acids inhibit fungal eumelanin in the human pathogen Aspergilius flavus (117). Incidentally, this class of compounds is patented for use in human cosmetics, and are marketed as solutions to inhibit melanogenesis in the skin (118,119).…”