<i>Lomentospora prolificans</i> synthesizes several types of melanin

<i>Lomentospora prolificans</i> is a filamentous fungus with a global distribution, exhibiting a particularly higher prevalence in human-impacted environments. Melanins are biological compounds with important functions that contribute to the virulence of many pathogenic fungi. Like many fungi, <i>L. prolificans</i> produces melanin, but little is known about its structure and composition. In the current study, we characterized <i>L. prolificans</i>-associated melanin using chemical, biological, biophysical, and structural techniques while also assessing the impact of inhibitors of distinct melanization pathways. Our results reveal that this pathogenic fungus produces multiple types of melanin pigments and suggest the possibility of a new type of melanin, which is synthesized together with a mixture of DHN-, DOPA-, and pyomelanin types.IMPORTANCEThis fungal species is associated with a wide spectrum of human infections, especially in immunosuppressed individuals, for whom it causes severe and debilitating illnesses with high morbidity and mortality that are compounded by its pan-resistant profile with respect to antifungal drugs. Melanin is a ubiquitous pigment among fungi with a broad range of actions that include promoting fungal virulence. Although melanin is one of the most studied virulence factors in pathogenic fungi, relatively little is known about the chemistry of this pigment in <i>L. prolificans</i>. These insights enhance our understanding of <i>L. prolificans'</i> virulence mechanisms, paving the way for potential therapeutic interventions.