(3S)-2,3-epoxy-2,3-dihydrosqualene

2,3-oxidosqualene is a linear C30 triterpenoid intermediate in the biosynthetic pathway of sterols and various triterpenoid saponins [1]. It is synthesized from squalene through the regio and stereospecific oxygenation of one of its double bonds, a reaction catalyzed by squalene epoxidase (SE) [42, 43]. This reaction introduces an oxygen atom across the C=C double bond, generating the characteristic epoxide group of 2,3-oxidosqualene [43]. As a central committed precursor, 2,3-oxidosqualene undergoes complex cyclization reactions mediated by oxidosqualene cyclases (OSCs), which generate transient cationic intermediates such as dammarenyl or protosteryl cations [1]. Before cyclization, the molecule adopts specific folded conformations that facilitate the formation of distinct cyclic products, including a chair-boat-chair-boat conformation during sterol biosynthesis and a chair-chair-chair-boat conformation during triterpene biosynthesis [1]. In some organisms, 2,3-oxidosqualene is produced from isopentenyl diphosphate and dimethylallyl diphosphate through the sequential activities of farnesyl diphosphate synthase, squalene synthase, and squalene epoxidase [48].

2,3-oxidosqualene serves as a critical metabolic branch point for the heterologous production of bioactive triterpenoids, including ginsenosides and aglycones such as protopanaxadiol and oleanolic acid [1, 48]. Metabolic engineering strategies aimed at increasing triterpenoid production commonly focus on enhancing the intracellular availability of 2,3 oxidosqualene through the overexpression of upstream enzymes, including 3-hydroxy-3-methylglutaryl-CoA reductase, squalene synthase, and squalene epoxidase [1, 48]. Carbon flux can also be redirected toward specific target products by reducing competing reactions that consume 2,3-oxidosqualene, including those catalyzed by cycloartenol synthase [1]. Furthermore, the selection and expression of different squalene epoxidase isoforms can influence the availability of 2,3-oxidosqualene and thereby regulate the synthesis of specific triterpene and phytosterol products [1].