Dataset Information

Microbial biotransformation of DON: molecular basis for reduced toxicity.

ABSTRACT: Bacteria are able to de-epoxidize or epimerize deoxynivalenol (DON), a mycotoxin, to deepoxy-deoxynivalenol (deepoxy-DON or DOM-1) or 3-epi-deoxynivalenol (3-epi-DON), respectively. Using different approaches, the intestinal toxicity of 3 molecules was compared and the molecular basis for the reduced toxicity investigated. In human intestinal epithelial cells, deepoxy-DON and 3-epi-DON were not cytotoxic, did not change the oxygen consumption or impair the barrier function. In intestinal explants, exposure for 4?hours to 10??M DON induced intestinal lesions not seen in explants treated with deepoxy-DON and 3-epi-DON. A pan-genomic transcriptomic analysis was performed on intestinal explants. 747 probes, representing 323 genes, were differentially expressed, between DON-treated and control explants. By contrast, no differentially expressed genes were observed between control, deepoxy-DON and 3-epi-DON treated explants. Both DON and its biotransformation products were able to fit into the pockets of the A-site of the ribosome peptidyl transferase center. DON forms three hydrogen bonds with the A site and activates MAPKinases (mitogen-activated protein kinases). By contrast deepoxy-DON and 3-epi-DON only form two hydrogen bonds and do not activate MAPKinases. Our data demonstrate that bacterial de-epoxidation or epimerization of DON altered their interaction with the ribosome, leading to an absence of MAPKinase activation and a reduced toxicity.

SUBMITTER: Pierron A

PROVIDER: S-EPMC4933977 | biostudies-literature | 2016 Jul

REPOSITORIES: biostudies-literature

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Microbial biotransformation of DON: molecular basis for reduced toxicity.

Pierron Alix A Mimoun Sabria S Murate Leticia S LS Loiseau Nicolas N Lippi Yannick Y Bracarense Ana-Paula F L AP Schatzmayr Gerd G He Jian Wei JW Zhou Ting T Moll Wulf-Dieter WD Oswald Isabelle P IP

Scientific reports 20160706

Bacteria are able to de-epoxidize or epimerize deoxynivalenol (DON), a mycotoxin, to deepoxy-deoxynivalenol (deepoxy-DON or DOM-1) or 3-epi-deoxynivalenol (3-epi-DON), respectively. Using different approaches, the intestinal toxicity of 3 molecules was compared and the molecular basis for the reduced toxicity investigated. In human intestinal epithelial cells, deepoxy-DON and 3-epi-DON were not cytotoxic, did not change the oxygen consumption or impair the barrier function. In intestinal explant ...[more]

PMID: 27381510

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Project description:Electron and charge transfers are part of many vital processes in nature and technology. Ab initio descriptions of these processes provide useful insights that can be utilized for applications. A combination of the embedded cluster material model and nonorthogonal configuration interaction (NOCI), in which the cluster wave functions are expanded in many-electron basis functions (MEBFs) consisting of spin-adapted, antisymmetrized products of multiconfigurational wave functions of fragments (which are usually molecules) in the cluster, appears to provide a compromise between accuracy and calculation time. Additional advantages of this NOCI-Fragments approach are the chemically convenient interpretation of the wave function in terms of molecular states, and the direct accessibility of electronic coupling between diabatic states to describe energy and electron transfer processes. Bottlenecks in this method are the large number of two-electron integrals that have to be handled for the calculation of an electronic coupling matrix element and the enormous number of matrix elements over determinant pairs that have to be evaluated for the calculation of one matrix element between the MEBFs. We show here how we created a reduced common molecular orbital basis that is utilized to significantly reduce the number of two-electron integrals that need to be handled. The results obtained with this basis do not show any loss of accuracy in relevant quantities like electronic couplings and vertical excitation energies. We also show a significant reduction in computation time without loss in accuracy when matrix elements over determinant pairs with small weights are neglected in the NOCI. These improvements in the methodology render NOCI-Fragments to be also applicable to treat clusters of larger molecular systems with larger atomic basis sets and larger active spaces, as the computation time becomes dependent on the number of occupied orbitals and less dependent on the size of the active space.

Dataset Information

Microbial biotransformation of DON: molecular basis for reduced toxicity.

Publications

Microbial biotransformation of DON: molecular basis for reduced toxicity.

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