Mining Genetically Encoded Biosensors from Filamentous Fungi

Genetically encoded biosensors represent cutting-edge biosensors due to their capabilities in real-time monitoring and precise control in living cells. However, the development of eukaryotic genetically encoded biosensors for new analytes is constrained by the shortage of signal-receptor pairs. Bacterial biosensors have been transferred to eukaryotes to expand the signal detection space, which has achieved remarkable success. However, due to the significant differences between eukaryotic and prokaryotic gene expression systems, optimizing bacterial biosensors has proven challenging. Successful cases indicate that developing orthogonal signal-receptor pairs directly from eukaryotic systems may offer a viable solution. Indeed, the potential of filamentous fungi-a highly diverse group of organisms that share conserved as well as specific signaling and metabolic pathways with yeast and mammalian cells-has been largely overlooked in biosensor development. In this review, we systematically examine biosensing systems in filamentous fungi, summarize their signal recognition receptors, signal transduction pathways, responsive transcription factors, and provide an overview of the biosensors and synthetic tools developed from them. Finally, we highlight the promise and challenges of biosensor development from filamentous fungi and discuss their potential applications.