According to a debated hypothesis, the biosynthesis from emodin of the medicinally important natural compound hypericin is catalyzed in St John's wort (Hypericum perforatum) by the phenolic oxidative-coupling protein Hyp-1. Recombinant St John's wort Hyp-1 has been overexpressed in Escherichia coli and obtained in single-crystal form. The crystals belong to the orthorhombic system, space group P2(1)2(1)2(1), with unit-cell parameters a = 37.5, b = 76.7, c = 119.8 A, contain two protein molecules in the asymmetric unit and diffract X-rays to 1.73 A resolution.