Yeast-secreted compounds with antifungal activity-screening, genetic parts, biosynthetic pathways, and regulation

Awareness is rising that antifungal resistance poses a threat to agriculture, food safety, biodiversity, and human health. There is a limited number of antifungals available and resistance to all of them has been reported. The development of novel antifungals is complex, as eukaryotic organisms have very few selective drug targets that distinguish them from the infected plant, human, or animal host. Yeasts produce different compounds with antifungal activity, ranging from small molecules such as iron chelators, biosurfactants, and volatile organic compounds, to proteins like myocins and hydrolytic enzymes. Those could be further developed into new antifungals; however, there is a scarcity of fundamental knowledge on their chemical structure, their mode of action, their biosynthesis, and its regulation. Given the opportunities that yeasts display as industrial hosts and the synthetic biology tools available, a deeper understanding of these molecular aspects could enable a wider range of yet underexplored applications for the producer yeast and their molecules, from biocontrol to food preservation and human health. To facilitate this exploration, we here consolidate current molecular knowledge on these compounds, suggest readily available methodologies to screen for different molecule classes in natural yeast isolates and discuss how they could be further studied and engineered towards their eventual application.