Computational approaches to investigate biological and chemical foodborne threats: exploring mechanisms of action and bioremediation strategies

This PhD thesis frames into the field of Food Science and revolves around computational approaches, and their fit-for-purpose integration with experimental analysis, to tackle biological and chemical foodborne threats, as the title suggests, with two main objectives. The first one is to elucidate the mechanism of action of certain chemicals relevant to food safety and/or ecotoxicology, gaining more structural insights through molecular modelling-based studies, being critical for their risk assessment and subsequent management. The pipelines applied led to the unveiling of new possible targets for several compounds relevant to food safety and environmental health or to further clarify their mechanisms of action, metabolism, pharmaco/toxico-dynamic and -kinetic. The second objective aimed at identifying natural compounds possibly able to mitigate foodborne pathogens growth or action, not only in humans but also in animals and crops. The thesis is organized in four Sections, as detailed below. Section I reports a general introduction on the state of art of computational approaches in food science with a special focus on food chemistry and microbiology, and those associated aspects that are relevant to food hygiene. Moreover, it introduces briefly the methodologies used within the several case-studies reported in this PhD thesis. In the second part, the focus was moved to foodborne pathogens and chemical foodborne threats and on how computational approaches can deal with them also considering a One Health framework. Section II focuses on foodborne pathogens, specifically Hepatitis E Virus, Listeria monocytogenes and Campylobacter jejuni. Here, in the context of developing anti-viral/bacterial strategies, computational approaches were applied to study virulence factors and proposing natural compounds possibly acting against them. Section III reports a case-study regarding bioremediation. Here a hybrid in silico – in vitro approach was applied to find cytochromes able to hydroxylate an emerging mycotoxin, fusaric acid, whose hydroxylation is known to lower its phytotoxic action. Section IV contains five chapters proposing new mechanistic insights on xenobiotics, either regarding their mechanism of action, possible structural insights on their metabolism and bioactivation or lastly new possible targets underpinning their action in living organisms. Eventually, section V contains a conclusion based on the insights obtained during this three year-long PhD journey and a discussion of possible outlooks.