Selective Phosphorylation of Phenols and Benzenediols by the Kinase PsiK and Variants Thereof
Angewandte Chemie International Edition June 17, 2025 Ahram Kim, Nicolás M. Morato, Prabir Saha et al. 4 citations
The enzyme PsiK, which selectively phosphorylates psilocin during psilocybin biosynthesis in Psilocybe cubensis, can also phosphorylate a wide range of substituted phenols and benzenediols beyond its natural substrate. This expands the scope of biocatalytic phosphorylation for synthetic chemistry. Active site mutations further broaden substrate scope and improve site-selectivity, with engineering expedited by DESI-MS screening that analyzed 2688 reactions in 40 minutes. Gram-scale phosphorylation of a representative substrate achieved a turnover number over 10,000. These results highlight PsiK's utility for selective phosphorylation under mild conditions.