Dataset Information

The enzymatic detoxification of the mycotoxin deoxynivalenol: identification of DepA from the DON epimerization pathway.

ABSTRACT: The biological detoxification of mycotoxins, including deoxynivalenol (DON), represents a very promising approach to address the challenging problem of cereal grain contamination. The recent discovery of Devosia mutans 17-2-E-8 (Devosia spp. 17-2-E-8), a bacterial isolate capable of transforming DON to the non-toxic stereoisomer 3-epi-deoxynivalenol, along with earlier reports of bacterial species capable of oxidizing DON to 3-keto-DON, has generated interest in the possible mechanism and enzyme(s) involved. An understanding of these details could pave the way for novel strategies to manage this widely present toxin. It was previously shown that DON epimerization proceeds through a two-step biocatalysis. Significantly, this report describes the identification of the first enzymatic step in this pathway. The enzyme, a dehydrogenase responsible for the selective oxidation of DON at the C3 position, was shown to readily convert DON to 3-keto-DON, a less toxic intermediate in the DON epimerization pathway. Furthermore, this study provides insights into the PQQ dependence of the enzyme. This enzyme may be part of a feasible strategy for DON mitigation within the near future.

SUBMITTER: Carere J

PROVIDER: S-EPMC6196400 | biostudies-literature | 2018 Nov

REPOSITORIES: biostudies-literature

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The enzymatic detoxification of the mycotoxin deoxynivalenol: identification of DepA from the DON epimerization pathway.

Carere Jason J Hassan Yousef I YI Lepp Dion D Zhou Ting T

Microbial biotechnology 20171117 6

The biological detoxification of mycotoxins, including deoxynivalenol (DON), represents a very promising approach to address the challenging problem of cereal grain contamination. The recent discovery of Devosia mutans 17-2-E-8 (Devosia spp. 17-2-E-8), a bacterial isolate capable of transforming DON to the non-toxic stereoisomer 3-epi-deoxynivalenol, along with earlier reports of bacterial species capable of oxidizing DON to 3-keto-DON, has generated interest in the possible mechanism and enzyme ...[more]

PMID: 29148251

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Project description:BackgroundFeedgrain contamination with mycotoxins, including deoxynivalenol (DON, "vomitoxin") is relatively frequently encountered. Pigs are particularly sensitive to the toxicity of DON. To assess the interplay between DON and porcine reproductive and respiratory syndrome virus (PRRSV), we performed an experimental DON exposure-PRRSV vaccination-challenge infection trial. Three-week-old piglets were divided into four groups. Groups I, II and III (10 animals/group) were vaccinated with a PRRSV modified live vaccine and 2 weeks later challenged with a heterologous field strain. While group I was not supplemented with DON, animals in groups II and III received DON for 4 weeks prior to challenge infection at levels that can be encountered in pig feed, employing a low-dose or high-dose regime (group II: 40 µg DON/kg body weight per day; group III: 80 µg DON/kg body weight per day, corresponding to approx. 1 or 2 mg DON/kg feed, respectively). Eight animals (group IV; unvaccinated, not DON exposed) served as control animals for the challenge infection.ResultsWe assessed clinical signs, virus load in serum and various organs as well as antibody titres in the animals. All vaccinated animals mounted an efficient PRRSV-specific antibody response within 2 weeks, except for 20% of the animals receiving the higher DON dose. Upon virus challenge, the vaccinated animals in group I were protected from clinical signs. Vaccinated DON-exposed animals in group II and III were protected from clinical signs to a lesser extent. Clinical signs in group III receiving the higher dose of DON were as severe as in the (unvaccinated, not DON exposed) control group IV. The animals of group III also displayed lower antibody titres compared with the animals in group I and II.ConclusionsThe experimental vaccination/challenge study therefore revealed that exposure of pigs to DON for a period of 4 weeks deteriorates the efficacy of vaccination against clinical signs of PRRS.

Project description:The Fusarium mycotoxin deoxynivalenol (DON) is a frequent contaminant of cereal-based food and feed. Mammals metabolize DON by conjugation to glucuronic acid (GlcAc), the extent and regioselectivity of which is species-dependent. So far, only DON-3-glucuronide (DON-3-GlcAc) and DON-15-GlcAc have been unequivocally identified as mammalian DON glucuronides, and DON-7-GlcAc has been proposed as further DON metabolite. In the present work, qualitative HPLC-MS/MS analysis of urine samples of animals treated with DON (rats: 2 mg/kg bw, single bolus, gavage; mice: 1 mg/kg bw, single i.p. injection; pigs: 74 µg/kg bw, single bolus, gavage; cows: 5.2 mg DON/kg dry mass, oral for 13 weeks) revealed additional DON and deepoxy-DON (DOM) glucuronides. To elucidate their structures, DON and DOM were incubated with human (HLM) and rat liver microsomes (RLM). Besides the expected DON/DOM-3- and 15-GlcAc, minor amounts of four DON- and four DOM glucuronides were formed. Isolation and enzymatic hydrolysis of four of these compounds yielded iso-DON and iso-DOM, the identities of which were eventually confirmed by NMR. Incubation of iso-DON and iso-DOM with RLM and HLM yielded two main glucuronides for each parent compound, which were isolated and identified as iso-DON/DOM-3-GlcAc and iso-DON/DOM-8-GlcAc by NMR. Iso-DON-3-GlcAc, most likely misidentified as DON-7-GlcAc in the literature, proved to be a major DON metabolite in rats and a minor metabolite in pigs. In addition, iso-DON-8-GlcAc turned out to be one of the major DON metabolites in mice. DOM-3-GlcAc was the dominant DON metabolite in urine of cows and an important DON metabolite in rat urine. Iso-DOM-3-GlcAc was detected in urine of DON-treated rats and cows. Finally, DON-8,15-hemiketal-8-glucuronide, a previously described by-product of DON-3-GlcAc production by RLM, was identified in urine of DON-exposed mice and rats. The discovery of several novel DON-derived glucuronides in animal urine requires adaptation of the currently used methods for DON-biomarker analysis.

Dataset Information

The enzymatic detoxification of the mycotoxin deoxynivalenol: identification of DepA from the DON epimerization pathway.

Publications

The enzymatic detoxification of the mycotoxin deoxynivalenol: identification of DepA from the DON epimerization pathway.

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