Advances in Fungal Genetic Manipulation: From Conventional Systems to Historically Intractable Fungi

Dear Colleagues,

Fungal genetics has long relied on well-established advances grounded in a small set of classical, genetically tractable, model organisms such as Saccharomyces cerevisiae, Neurospora crassa, and Aspergillus nidulans. Studies using these methodologies have provided important insights into fungal biology, namely gene regulation, metabolism, development, and pathogen–host interactions. Recent cutting-edge genetic breakthroughs have broadened the range of species accessible to genetic manipulation. As these new tools emerge, fungal research is shifting toward an increasingly diverse array of non-conventional taxa, many of which were historically considered intractable due to their physiological complexity, slow growth, unusual reproductive strategies, or limited molecular tractability.

Among these groups, dimorphic pathogenic fungi—including Blastomyces, Sporothrix, Histoplasma, Coccidioides and Paracoccidioides species—have historically posed, and in some cases still pose, substantial challenges in relation to genetic manipulation. Their dual morphological states, pathogenic lifestyles, and limited availability of efficient transformation systems continue to hinder the development of robust reverse-genetics platforms. Basidiomycetes, on the other hand, present a different layer of complexity. The presence of multiple nuclei within mycelial cells, frequent heterokaryosis, and dikaryotic life cycles add significant constraints to genome editing strategies, making these species considerably more difficult to engineer than classical ascomycete models. Furthermore, industrially relevant species, oleaginous fungi, and symbiotic or extremotolerant lineages represent vast reservoirs of unexplored biological diversity. Their genomes encode unique metabolic capabilities, unconventional developmental programs, and ecological strategies that often fall outside established paradigms. Yet, precisely because of their biological distinctiveness, these organisms have remained largely recalcitrant to genetic modification, limiting our ability to interrogate or exploit their full potential.

During recent years, technological progress has been central to redefining what is now possible. Advances in genome sequencing, comparative genomics, functional transcriptomics, and multi-omics integration have provided unprecedented resolution for identifying candidate genes, pathways, and regulatory networks. This technological progress has enhanced our capacity to interrogate gene function even in species previously lacking robust genetic frameworks. These developments have enabled novel investigations into fungal physiology, adaptations, secondary metabolism, environmental sensing, and interspecies interactions.

This Special Issue aims to capture the state of the field expanding the boundaries of fungal genetic manipulation. We welcome contributions that explore the following:

• New insights into genetic and regulatory systems in both established models and non-conventional fungi;
• Conceptual advances in molecular and systems-level approaches applied across diverse fungal taxa;
• Studies revealing unique biological processes in basidiomycetes, early-diverging fungi, dimorphic pathogens, symbionts, and extremotolerant species;
• Frameworks that address longstanding challenges associated with historically difficult-to-study fungal organisms.

By bringing together work across traditional and non-traditional fungi, this Special Issue seeks to highlight both the depth and the breadth of current capabilities, while also identifying conceptual gaps and opportunities that will shape the future of fungal biology. We invite researchers from all areas of fungal science to contribute original articles, reviews, perspectives, and commentaries that collectively advance our understanding of fungal genetic manipulation and broaden the spectrum of species accessible to meaningful molecular investigation.

Dr. Fernando José Santos Rodrigues
Guest Editor

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• fungal genetics
• intractable fungi
• fungal gene editing
• fugal pathogenesis