Metabolism can be distinguished into primary and secondary metabolism, with the former sustaining the living state and growth of the cell, while the latter is involved in the production of metabolites that can have niche-specific functions but are not required for the immediate survival of the cell. Secondary metabolism is intrinsically linked to primary metabolism, which directly controls basic cellular traits such as the uptake and secretion of macromolecules. In fungi, this secretory activity exports the machinery required for nutrient acquisition (hydrolysis and uptake; nevertheless, also a vast array of secondary metabolites (SM), which are of great interest for biotechnological and biomedical applications. Furthermore, primary metabolism also contributes to fungal virulence, including the composition of fungal cell wall structure and the export of virulence factors, both of which have been shown to contribute immune-modulatory and -evasive properties during invasion of mammalian hosts. Rooted in the paradigm of unity of primary metabolism, the molecular basis for primary metabolism in is highly conserved allowing the investigation of species-specific traits and developing fungi as experimental models to study human diseases.

Fungal primary metabolism has been mainly explored and manipulated for biotechnological applications, with the most famous examples notably being ethanol production by the yeast Saccharomyces cerevisiae or citric acid production by the filamentous fungus Aspergillus niger. SM biosynthesis and secretion has also received a lot of attention in recent years, including the screening of fungal genomes for gene biosynthetic clusters encoding novel SMs and the identification of regulatory mechanisms underlying SM production. Despite this increased interest in fungal natural products, a substantial amount of research remains to be undertaken in order to fully understand SM identification, function, and exploration for biomedical applications. In addition, fungal primary metabolism and its regulatory role in the expression of different virulence traits has been largely neglected. A recent study described how glucose metabolism and its regulation by different protein kinases can affect cell wall architecture in Aspergillus fumigatus, highlighting the importance of primary metabolism for the production and employment of virulence factors.

The aim of this Research Topic is to investigate primary and secondary metabolism in fungi implicated as causal agents of disease in human and plants, and elucidate and characterize these mechanisms in the context of virulence. We welcome Original Research papers that investigate the identification and production of primary and secondary metabolites and their relevance for fungal virulence. We also accept papers that use fungi to model mammalian metabolic diseases. Subtopics include:

• Understanding primary metabolism through the investigation of regulatory mechanisms
• Primary metabolism and its impact on virulence traits
• Identification of secondary metabolites
• Regulatory mechanisms underlying secondary metabolite production
• Using fungi as models for metabolism-related diseases in plants and mammals including humans

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Frontiers in Microbiology

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