Solanesyl diphosphate synthase (SPS) (SPS)

Solanesyl diphosphate synthase (SPS) is a key enzyme in the isoprenoid biosynthetic pathway, responsible for synthesizing the long-chain polyprenyl diphosphate precursor (C45) used in the production of ubiquinone (Coenzyme Q9) and plastoquinone-9 [2, 16]. In humans, the functional equivalent is the heterotetrameric decaprenyl diphosphate synthase (composed of PDSS1 and PDSS2 subunits), which produces the C50 side chain for Coenzyme Q10 [10, 11]. SPS catalyzes the successive head-to-tail condensation of isopentenyl diphosphate (IPP) units onto an allylic primer such as farnesyl diphosphate (FPP) or geranylgeranyl diphosphate (GGPP) [16]. As a therapeutic target, SPS is particularly significant in the context of infectious diseases and agriculture. In protozoan parasites like Trypanosoma brucei, inhibition of SPS depletes ubiquinone pools, disrupting mitochondrial electron transport and leading to parasite death [3, 6]. In plants, SPS is the molecular target of the herbicide aclonifen, which causes bleaching by interfering with plastoquinone-dependent carotenoid biosynthesis [4, 18]. In humans, genetic mutations in the PDSS subunits lead to primary Coenzyme Q10 deficiency, a severe multisystem disorder characterized by encephalopathy and nephrotic syndrome, highlighting the enzyme's critical role in cellular respiration and antioxidant defense [10, 11]. PDSS2 has also been identified as a candidate tumor suppressor, with its downregulation linked to increased cell proliferation in certain cancers [10, 14].

Other names

All-trans-nonaprenyl-diphosphate synthasePDSS1PDSS2SPPStrans-octaprenyltranstransferaseSolanesyl-diphosphate synthase subunit 1Solanesyl-diphosphate synthase subunit 2

Inhibition of the enzyme prevents the synthesis of the polyprenyl side chain of ubiquinone and plastoquinone, leading to the disruption of the mitochondrial electron transport chain, increased production of reactive oxygen species, and impaired cellular respiration.