Biosynthesis of AS2077715 and Funiculosin: Pathway Reconstitution and Identification of Enzymes that Form the All- cis Cyclopentanetetraol Moiety.

The complete biosynthetic pathways of the potent antifungals AS2077715 ( 1 ) and funiculosin ( 2 ) are reconstituted and characterized. A five-enzyme cascade, including a multifunctional flavin-dependent monooxygenease and a repurposed O- methyltransferase, is involved to perform the dearomatization, stereoselective ring contraction, and redox transformations to morph a hydroxyphenyl-containing precursor into the unusual all- cis cyclopentanetetraol moiety.