Oxidosqualene Cyclase Second‐Sphere Residues Profoundly Influence the Product Profile

Cycloartenol synthase converts oxidosqualene to the pentacyclic triterpene alcohol cycloartenol. Mutations at His477 dramatically alter the product profile. However, these changes are catalytically irrelevant in the presence of Tyr410Thr and Ile481Val mutations. Modeling studies have established that His477 is a second-sphere residue that affects catalysis indirectly through its interactions with the active-site residue Tyr410.