Regioselective Hydroxylation of Stilbenes by White-Rot Fungal P450s Enables Preparative-Scale Synthesis of Stilbenoids

Scaling up biocatalytic reactions involving cytochrome P450 monooxygenases (P450s) is challenging due to their instability, low substrate loading, co-factor, and oxygen requirements as well as the dependency on a reductase partner, which limits their integration into synthetic chemistry. Recently, a biocatalytic study investigated frequently used bacterial P450s to produce bioactive stilbenoids, extending the repertoire of sustainable synthetic strategies with remarkable success. This article explores the complementary application of less common eukaryotic P450s as a viable alternative for generating the same compounds when employed as a Pichia pastoris-based wholecell biocatalyst. In a direct comparison to their bacterial equivalents, the recently discovered P450s CYP5035S7 and CYP5035S9 from the white-rot fungus Polyporus arcularius are shown to be competitively efficient at synthesising stilbenoids at preparative-scale.