RT journal article T1 Timing Is Everything: The Fungal Circadian Clock as a Master Regulator of Stress Response and Pathogenesis A1 Coca Ruiz, Víctor A1 Boy Ruiz, Daniel A2 Química Orgánica K1 circadian rhythm K1 fungi K1 stress response K1 oxidative stress K1 osmotic stress K1 pathogenesis K1 chronobiology K1 Neurospora crassa K1 clock-controlled genes K1 chrono-fungicides AB Fungi, from saprophytes to pathogens, face predictable daily fluctuations in light, temperature, humidity, and nutrient availability. To cope, they have evolved an internal circadianclock that confers a major adaptive advantage. This review critically synthesizes currentknowledge on the molecular architecture and physiological relevance of fungal circadiansystems, moving beyond the canonical Neurospora crassa model to explore the broader phylogenetic diversity of timekeeping mechanisms. We examine the core transcription-translationfeedback loop (TTFL) centered on the FREQUENCY/WHITE COLLAR (FRQ/WCC) system and contrast it with divergent and non-canonical oscillators, including the metabolicrhythms of yeasts and the universally conserved peroxiredoxin (PRX) oxidation cycles. Acentral theme is the clock’s role in gating cellular defenses against oxidative, osmotic, andnutritional stress, enabling fungi to anticipate and withstand environmental insults throughproactive regulation. We provide a detailed analysis of chrono-pathogenesis, where the circadian control of virulence factors aligns fungal attacks with windows of host vulnerability,with a focus on experimental evidence from pathogens like Botrytis cinerea, Fusarium oxysporum, and Magnaporthe oryzae. The review explores the downstream pathways—includingtranscriptional cascades, post-translational modifications, and epigenetic regulation—thattranslate temporal signals into physiological outputs such as developmental rhythms inconidiation and hyphal branching. Finally, we highlight critical knowledge gaps, particularly in understudied phyla like Basidiomycota, and discuss future research directions. Thisincludes the exploration of novel clock architectures and the emerging, though speculative,hypothesis of “chrono-therapeutics”—interventions designed to disrupt fungal clocks—asa forward-looking concept for managing fungal infections. PB MDPI SN 2673-7140 YR 2025 FD 2025 LK http://hdl.handle.net/10498/39350 UL http://hdl.handle.net/10498/39350 LA eng DS Repositorio Institucional de la Universidad de Cádiz RD 06-nov-2026