Biosynthesis of Diphenyl Ethers in Fungi

A new and concise biosynthetic pathway of fungal diphenyl ethers (DPEs) has been elucidated and efficiently reconstructed in yeast. The pathway includes an unusual nonreducing polyketide synthase (NRPKS) responsible for the formation of a polyketide dimer with an ether bond linkage as well as two cofactor-independent enzymes that catalyze tandem regioselective decarboxylation reactions. Our discovery here opens a new window for utilizing fungal DPEs as a platform to design and synthesize analogues for the development of highly useful drug leads.