Nematode-Trapping Fungus Arthrobotrys oligospora is Hungry for UQ10 and COQ7 to Treat Iron Overload

Understanding the mechanisms behind food choice determination is crucial for elucidating speciation and interspecies interactions. Nematode-trapping fungi (NTF) develop complex trapping devices to capture nematodes as a food source under nutrient-deprived conditions. However, the specific requirements of NTFs for nematodes remain a subject of ongoing debate. In our investigation of environmental factors influencing the formation of iron-rich trapping devices, we found that elevated oxygen levels significantly enhanced the trapping devices of the dominant NTF, Arthrobotrys oligospora. Surprisingly, all NTFs lacked coq7, a key gene involved in ubiquinol (UQ) biosynthesis and iron chelation. Notably, A. oligospora utilizes UQ8 instead of UQ9-10 for low-aerobic respiration. Transcriptional, metabolic, mutational, and phenotypic analyses revealed that A. oligospora produces a chemotaxonomic class of highly oxygenated arthrobotrins, characterized by a UQ3 skeleton, for high-aerobic respiration. Disruption of arthrobotrin biosynthesis triggered UQ8 biosynthesis and resulted in a significant increase in trapping devices and nematicidal activity in the art mutant under elevated oxygen conditions. The addition of UQ10 to both wild-type and art mutants strongly inhibited trapping device development. Remarkably, the iron-rich trapping devices preferentially capture N2 nematodes that harbor iron-chelating COQ7 with ferritin property. Time-calibrated evolutionary analysis combined with historical geological changes, indicated that the NTF ancestor lost the coq7 gene after acquiring the arthrobotrin biosynthetic gene cluster during the "superoligotrophy" with dramatic shifts in global oxygen levels and temperature changes. Our results demonstrate that oxygen is a critical factor shaping the genomic, metabolic, morphological, and behavioral adaptations of NTFs, illuminating the role of the coq7 loss in the origin and evolution of trapping devices and their predatory behavior. Our findings suggested that NTF is an effective eukaryotic model for elucidating a new mechanism for excess iron production and for investigating iron chelation therapy.