Novel insights into the specialized metabolism of the extremophile black yeast Hortaea werneckii and its modulation, unlocking its potential for compound discovery

Hortaea werneckii is a halotolerant yeast, found in various habitats and which specialized metabolism remains largely unexplored. Moreover, its chemical response to high salinities has not been thoroughly investigated. To address this gap, a large-scale metabolomic study based on HPLC-HRMS/MS was conducted on 64 strains, collected from different habitats worldwide, and cultivated both on saline and non-saline media. The culture media salinity significantly modulated the strains metabolomes, suggesting the yeast exhibits a specific chemical response to high salt concentrations, potentially linked to halotolerance mechanisms. Additionally, the metabolomes were influenced by the ecological origin of the strains, with opportunistic pathogenic isolates producing distinct metabolites. Molecular networking revealed that H. werneckii synthesizes various chemical classes, including potential cytotoxic compounds, making this yeast a potentially interesting source of bioactive compounds. Hortein was detected as dominant and ubiquitous, emerging as a potential chemical marker for the species. This study highlights several compounds of interest, related to the chemical ecology and pathogenicity of H. werneckii. As most of them remain unidentified, future research should prioritize their isolation and identification, to improve our understanding of this extremophile organism and harness its potential in natural product discovery.