Biosynthesis of Prelycopersene Pyrophosphate and Lycopersene by Squalene Synthetase

Stereochemistry of trans-phytoene synthesis. Lycopersene as a carotene precursor and a mechanism for the synthesis of cis- and trans-phytoene

“…The synthesis is easily accounted for since squalene synthetase, which will synthesize lycopersene from geranylgeranyl pyrosphate (Qureshi et al (1973)), is present in this carotene-synthesizing system (C. Subbarayan and H. C. Rilling, unpublished observation). One would need to invoke nonspecific dehydrogenation of lycopersene to account for its fortuitious incorporation into phytoene.…”

Squalene synthetase, inhibition by ammonium analogs of carbocationic intermediates in the conversion of presqualene diphosphate to squalene

“…Analysis by UV and liquid scintillation spectrometry26 gave a specific activity of 52.7 mCi/mmol. In a previous experiment using the same procedure, a sample of cold 13 (5.3 mg, 25%) was prepared from 15 mg (0.036 mmol) of 12: NMR (300 MHz, CDClj) 8.60 (br s, 1 H), 8.06(dd, / = 8.4 and 1.4 Hz, 1 H), 7.88 (m, 3 H), 7.54 (m, 2 ), 5.08 (m, 4 H, vinyl), 4.97 (d, J = 7.3 Hz, 1 H, vinyl coupled to C3'), 4.65 (m, 1 H, carbinyl), 4.19 (m, 1 H, carbinyl), 2.0 (m, 14 H, vinyl methylenes), 1.65 (s, 2 H, vinyl methylenes), 1.64 (s, 6 H, methyls), 1.56 (s, 15 H, methyls), 1.5-1.0 (unresolved cyclopropyl resonances), 1.20 ppm (s, 3 H, cyclopropyl methyl); IR (CC14) 2960, 2920, 2860, 1718, 1450, 1375, 1350, 1280, 1225, 1190, 1130, 1090 cm-1; UV (Xma" acetonitrile) 236 nm (i, 6.3 X 104).…”

“…Although several were proposed for reaction 1, there is little work which bears directly on this step.1,10 In contrast, several groups recognized that the reductive rearrangement of 2 to 3 could be rationalized in terms of the bond reorganizations typically observed for cyclopropylcarbinyl cations."' 15 Rilling and co-workers13 originally proposed the sequence shown in Scheme I. Subsequently, Poulter et al 16 discovered that the rearrangement of primary cation 4 to tertiary cation 5 was neither kinetically nor thermodynamically favored in nonenzymatic model studies and concluded that squalene synthetase must exert strict regiocontrol on the cationic intermediates if the high selectivity required for biosysthesis of squalene was to be realized.…”

Conservation between Human and Fungal Squalene Synthetases: Similarities in Structure, Function, and Regulation

“…enzyme structure, because in the absence of NAD(P)H and the presence of Mn2 , the S. cerevisiae squalene synthetase forms dehydrosqualene from FPP (47). Furthermore, in the presence of both NAD(P)H and Mg2+, squalene synthetase converts GGPP inefficiently into the C40 analog of squalene (lycopersene) (33). It is thus possible that both synthetases are derived from a primordial dehydrosqualene synthetase, which acquired an NAD(P)H-binding pocket in the case of squalene synthetases and a modified isoprene-binding pocket in the case of phytoene synthetases.…”