Ochratoxin A: Molecular Interactions, Mechanisms of Toxicity and Prevention at the Molecular Level

Biosensing platforms based on peptide recognition provide a cost-effective and stable alternative to antibody-based capture and discrimination of ochratoxin-A (OTA) vs. ochratoxin-B (OTB) in monitoring bioassays. Attempts to engineer peptides with improved recognition efficacy require thorough structural and thermodynamic characterization of the binding-competent conformations. Classical molecular dynamics (MD) approaches alone do not provide a thorough assessment of a peptide’s recognition efficacy. In this study, in-solution binding properties of four different peptides, a hexamer (SNLHPK), an octamer (CSIVEDGK), NFO4 (VYMNRKYYKCCK), and a 13-mer (GPAGIDGPAGIRC), which were previously generated for OTA-specific recognition, were evaluated using an advanced MD simulation approach involving accelerated configurational search and predictive modeling. Peptide configurations relevant to ochratoxin binding were initially generated using biased exchange metadynamics and the dynamic properties associated with the in-solution peptide–ochratoxin binding were derived from Markov State Models. Among the various peptides, NFO4 shows superior in-solution OTA sensing and also shows superior selectivity for OTA vs. OTB due to the lower penalty associated with solvating its bound complex. Advanced MD approaches provide structural and energetic insights critical to the hapten-specific recognition to aid the engineering of peptides with better sensing efficacies.

“… 1 The dissociation constant (K D ) for ochratoxins was estimated from the average ΔG ° estimate using the Equation

K_{D} = \frac{1}{\exp (- \frac{Δ G}{R T})}

Section: Figurementioning

confidence: 99%

Evaluation of Ochratoxin Recognition by Peptides Using Explicit Solvent Molecular Dynamics

Thyparambil

Bazin²,

Guiseppi‐Elie

2017

“…OTA is nephrotoxic, carcinogenic, and a potent teratogen when tested in different mammalian models, and thereby is a potential risk to human health [10]. Several authors support that the mode of action of OTA implies the formation of covalent DNA adducts [11,12,13] and the increase of reactive oxygen species [14,15], hence these activities could explain the genotoxic and mutagenic activity of OTA.…”

Section: Introductionmentioning

confidence: 99%

Different Toxicity Mechanisms for Citrinin and Ochratoxin A Revealed by Transcriptomic Analysis in Yeast

Vanacloig-Pedros

Proft

Pascual-Ahuir

2016

Citrinin (CIT) and ochratoxin A (OTA) are important mycotoxins, which frequently co-contaminate foodstuff. In order to assess the toxicologic threat posed by the two mycotoxins separately or in combination, their biological effects were studied here using genomic transcription profiling and specific live cell gene expression reporters in yeast cells. Both CIT and OTA cause highly transient transcriptional activation of different stress genes, which is greatly enhanced by the disruption of the multidrug exporter Pdr5. Therefore, we performed genome-wide transcription profiling experiments with the pdr5 mutant in response to acute CIT, OTA, or combined CIT/OTA exposure. We found that CIT and OTA activate divergent and largely nonoverlapping gene sets in yeast. CIT mainly caused the rapid induction of antioxidant and drug extrusion-related gene functions, while OTA mainly deregulated developmental genes related with yeast sporulation and sexual reproduction, having only a minor effect on the antioxidant response. The simultaneous exposure to CIT and OTA gave rise to a genomic response, which combined the specific features of the separated mycotoxin treatments. The application of stress-specific mutants and reporter gene fusions further confirmed that both mycotoxins have divergent biological effects in cells. Our results indicate that CIT exposure causes a strong oxidative stress, which triggers a massive transcriptional antioxidant and drug extrusion response, while OTA mainly deregulates developmental genes and only marginally induces the antioxidant defense.

“…The former is considered to be a non-toxic compound, with a 10-times shorter elimination half-life than OTA [73]. …”

Section: Mycotoxin Biotransformation By Enzymesmentioning

confidence: 99%

Mycotoxin Biotransformation by Native and Commercial Enzymes: Present and Future Perspectives

Loi

Fanelli

Liuzzi

et al. 2017

170

146

Worldwide mycotoxins contamination has a significant impact on animal and human health, and leads to economic losses accounted for billions of dollars annually. Since the application of pre- and post- harvest strategies, including chemical or physical removal, are not sufficiently effective, biological transformation is considered the most promising yet challenging approach to reduce mycotoxins accumulation. Although several microorganisms were reported to degrade mycotoxins, only a few enzymes have been identified, purified and characterized for this activity. This review focuses on the biotransformation of mycotoxins performed with purified enzymes isolated from bacteria, fungi and plants, whose activity was validated in in vitro and in vivo assays, including patented ones and commercial preparations. Furthermore, we will present some applications for detoxifying enzymes in food, feed, biogas and biofuel industries, describing their limitation and potentialities.