Squalene--hopene cyclase (SHC)

Squalene--hopene cyclase (SHC) is a monotopic membrane-associated enzyme that catalyzes the extraordinary one-step cyclization of the linear triterpene squalene into pentacyclic hopene and, to a lesser extent, hopanol (diplopterol)[2][3][4][8]. This highly complex reaction forms five rings, nine stereocenters, and alters thirteen covalent bonds in a single enzymatic step[2][3]. SHC is widespread in bacteria and some plants, where it is essential for hopanoid biosynthesis—hopanoids are sterol-like molecules that help stabilize membranes, especially under stress[3][4]. The enzyme’s structure features a large, hydrophobic active-site cavity, lined with aromatic residues, and a nonpolar channel for substrate access[1][5]. Its mechanism is based on Brønsted acid catalysis, primarily utilizing an aspartate residue to initiate the polycyclization reaction cascade[4][5]. While SHC itself has not been directly targeted by clinically used drugs, it has been investigated as a template for developing antifungals and cholesterol-lowering agents due to its mechanistic and structural similarity to human oxidosqualene cyclase (lanosterol synthase)[4][6]. SHC serves as an important biocatalyst in synthetic chemistry for complex triterpene scaffolds[7].

Other names

Squalene hopene cyclaseSHCSqualene-hopanol cyclaseTriterpene cyclaseSQHC

Enzyme inhibitors (competitive active site binding), Transition-state analogs, Active-site-directed electrophiles[4].