Biaryl-Forming Enzymes from Aspergilli Exhibit Substrate-Dependent Stereoselectivity.

Natural biaryls typically occur as one regio- and atropisomeric variant in a given organism. Here, we report on the identification of biosynthetic genes of aurasperone- and bifonsecin-type biaryls in several Aspergillus species. The genes of the tailoring enzymes form a gene cluster that is separate from the polyketide synthase gene. Dimerization of naphthopyrone monomers is catalyzed by members of an undescribed subfamily of cytochrome P450 enzymes. The stereoselectivity of these enzymes is influenced by the two natural monomeric substrates; homodimerization of one monomer yields a stereochemically pure biaryl, while the other monomer yields a mixture of enantiomers.