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Beyond Ribosomal Binding: The Increased Polarity and Aberrant Molecular Interactions of 3- epi- deoxynivalenol

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ABSTRACT

Deoxynivalenol (DON) is a secondary fungal metabolite and contaminant mycotoxin that is widely detected in wheat and corn products cultivated around the world. Bio-remediation methods have been extensively studied in the past two decades and promising ways to reduce DON-associated toxicities have been reported. Bacterial epimerization of DON at the C3 carbon was recently reported to induce a significant loss in the bio-toxicity of the resulting stereoisomer (3-epi-DON) in comparison to the parental compound, DON. In an earlier study, we confirmed the diminished bio-potency of 3-epi-DON using different mammalian cell lines and mouse models and mechanistically attributed it to the reduced binding of 3-epi-DON within the ribosomal peptidyl transferase center (PTC). In the current study and by inspecting the chromatographic behavior of 3-epi-DON and its molecular interactions with a well-characterized enzyme, Fusarium graminearum Tri101 acetyltransferase, we provide the evidence that the C3 carbon epimerization of DON influences its molecular interactions beyond the abrogated PTC binding.

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Related in: MedlinePlus

Chromatographic separation of DON and 3-epi-DON. Both DON and 3-epi-DON were injected on Jupiter 4µ Proteo 90A HPLC column. The results indicated that DON (less-polar) eluted in a longer time frame (A) in comparison to 3-epi-DON (B) under the same isocratic separation conditions. Section (C) represents the injection of both compounds at the same run.
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toxins-08-00261-f002: Chromatographic separation of DON and 3-epi-DON. Both DON and 3-epi-DON were injected on Jupiter 4µ Proteo 90A HPLC column. The results indicated that DON (less-polar) eluted in a longer time frame (A) in comparison to 3-epi-DON (B) under the same isocratic separation conditions. Section (C) represents the injection of both compounds at the same run.

Mentions: The epimerization of DON at the C3 group rendered 3-epi-DON to a higher polarity spectrum compared to the parental compound, DON. Under the same isocratic separation conditions (buffer composition, temperature, reverse phase column), DON was originally eluting at 13.2 min. (Figure 2A) however after the bacterial epimerization, 3-epi-DON shifted to the 8.9 min. (Figure 2B). The noted change in elution time, despite the similarity in structures/molecular weights/ionization status, was an indicative of changes of the polarity index associated with electron rearrangements. Figure 2C evidently presents DON and 3-epi-DON separation patterns for Devosia mutans 17-2-E-8 LB broth sample under the same analytical conditions (isocratic) and using a reverse-phase C12 Jupiter 4µ Proteo 90A HPLC column (commonly used for the purification of peptide mixtures) which reflected an altered interactions of 3-epi-DON with the column matrix. While chromatographic separations are not conventionally used to draw conclusions about polarity changes of mycotoxins, the data presented here collectively supported the notions that the observed changes in elution times are due to the increased polarity of 3-epi-DON. Our experimental approach was similar to the one that was suggested earlier by Namjesnik-Dejanovic and Cabaniss [29].


Beyond Ribosomal Binding: The Increased Polarity and Aberrant Molecular Interactions of 3- epi- deoxynivalenol
Chromatographic separation of DON and 3-epi-DON. Both DON and 3-epi-DON were injected on Jupiter 4µ Proteo 90A HPLC column. The results indicated that DON (less-polar) eluted in a longer time frame (A) in comparison to 3-epi-DON (B) under the same isocratic separation conditions. Section (C) represents the injection of both compounds at the same run.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC5037487&req=5

toxins-08-00261-f002: Chromatographic separation of DON and 3-epi-DON. Both DON and 3-epi-DON were injected on Jupiter 4µ Proteo 90A HPLC column. The results indicated that DON (less-polar) eluted in a longer time frame (A) in comparison to 3-epi-DON (B) under the same isocratic separation conditions. Section (C) represents the injection of both compounds at the same run.
Mentions: The epimerization of DON at the C3 group rendered 3-epi-DON to a higher polarity spectrum compared to the parental compound, DON. Under the same isocratic separation conditions (buffer composition, temperature, reverse phase column), DON was originally eluting at 13.2 min. (Figure 2A) however after the bacterial epimerization, 3-epi-DON shifted to the 8.9 min. (Figure 2B). The noted change in elution time, despite the similarity in structures/molecular weights/ionization status, was an indicative of changes of the polarity index associated with electron rearrangements. Figure 2C evidently presents DON and 3-epi-DON separation patterns for Devosia mutans 17-2-E-8 LB broth sample under the same analytical conditions (isocratic) and using a reverse-phase C12 Jupiter 4µ Proteo 90A HPLC column (commonly used for the purification of peptide mixtures) which reflected an altered interactions of 3-epi-DON with the column matrix. While chromatographic separations are not conventionally used to draw conclusions about polarity changes of mycotoxins, the data presented here collectively supported the notions that the observed changes in elution times are due to the increased polarity of 3-epi-DON. Our experimental approach was similar to the one that was suggested earlier by Namjesnik-Dejanovic and Cabaniss [29].

View Article: PubMed Central - PubMed

ABSTRACT

Deoxynivalenol (DON) is a secondary fungal metabolite and contaminant mycotoxin that is widely detected in wheat and corn products cultivated around the world. Bio-remediation methods have been extensively studied in the past two decades and promising ways to reduce DON-associated toxicities have been reported. Bacterial epimerization of DON at the C3 carbon was recently reported to induce a significant loss in the bio-toxicity of the resulting stereoisomer (3-epi-DON) in comparison to the parental compound, DON. In an earlier study, we confirmed the diminished bio-potency of 3-epi-DON using different mammalian cell lines and mouse models and mechanistically attributed it to the reduced binding of 3-epi-DON within the ribosomal peptidyl transferase center (PTC). In the current study and by inspecting the chromatographic behavior of 3-epi-DON and its molecular interactions with a well-characterized enzyme, Fusarium graminearum Tri101 acetyltransferase, we provide the evidence that the C3 carbon epimerization of DON influences its molecular interactions beyond the abrogated PTC binding.

No MeSH data available.


Related in: MedlinePlus