Multiplex Base-Editing Enables Combinatorial Epigenetic Regulation for Genome Mining of Fungal Natural Products

, enabling the activation of eight cryptic gene clusters compared to the wild-type strains. A group of novel NPs harboring unique cichorine and polyamine hybrid chemical scaffolds were identified, which were not reported previously. We envision that our scalable and efficient MBE platform can be readily applied in other filamentous fungi for the genome mining of novel NPs, providing a powerful approach for the exploitation of fungal chemical diversity.