80995-97-7Relevant articles and documents
Discovery and Engineering of Bacterial (?)-Isopiperitenol Dehydrogenases to Enhance (?)-Menthol Precursor Biosynthesis
Zhan, Jing-Ru,Shou, Chao,Zheng, Yu-Cong,Chen, Qi,Pan, Jiang,Li, Chun-Xiu,Xu, Jian-He
supporting information, p. 3973 - 3982 (2021/07/02)
Microbial synthesis of (?)-menthol, a compound of plant origin, is of great importance because of the high demand for this product and related sustainability issues. However, the total biosynthesis of (?)-menthol from easily available feedstocks like (?)-limonene by engineered microbial hosts is stalled by the poor protein expression or activity of several enzymes from the native (?)-menthol biosynthesis pathway of mint (Mentha piperita). Among these unsatisfied steps, (?)-isopiperitenol dehydrogenase (IPDH) catalyzed oxidation reaction of (?)-trans-isopiperitenol was one of the bottlenecks that need to be optimized. In this work, two novel bacterial enzymes with IPDH activity were discovered to replace their inefficient counterpart from plant cells in microbial (?)-menthol synthesis. Two key residues in PaIPDH from Pseudomonas aeruginosa were mutated to PaIPDHE95F/Y199V with 4.4-fold improved specific activity than PaIPDH. The mechanism for the beneficial mutations was elucidated by molecular dynamics simulations. PaIPDHE95F/Y199V was used to synthesize (?)-isopiperitenone from (?)-limonene in vivo via a self-sufficient cofactor cascade enzyme reaction, affording a 3.7-fold enhanced titer of (?)-isopiperitenone compared with that obtained using the original mint IPDH (MpIPDH). The bacterial enzyme PaIPDHE95F/Y199V can be applied in the future for constructing a more efficient artificial pathway to biosynthesize (?)-menthol in a microbial whole-cell system. (Figure presented.).
Chemoenzymatic Synthesis of the Intermediates in the Peppermint Monoterpenoid Biosynthetic Pathway
Cheallaigh, Aisling Ní,Mansell, David J.,Toogood, Helen S.,Tait, Shirley,Lygidakis, Antonios,Scrutton, Nigel S.,Gardiner, John M.
supporting information, p. 1546 - 1552 (2018/08/04)
A chemoenzymatic approach providing access to all four intermediates in the peppermint biosynthetic pathway between limonene and menthone/isomenthone, including noncommercially available intermediates (-)-trans-isopiperitenol (2), (-)-isopiperitenone (3), and (+)-cis-isopulegone (4), is described. Oxidation of (+)-isopulegol (13) followed by enolate selenation and oxidative elimination steps provides (-)-isopiperitenone (3). A chemical reduction and separation route from (3) provides both native (-)-trans-isopiperitenol (2) and isomer (-)-cis-isopiperitenol (18), while enzymatic conjugate reduction of (-)-isopiperitenone (3) with IPR [(-)-isopiperitenone reductase)] provides (+)-cis-isopulegone (4). This undergoes facile base-mediated chemical epimerization to (+)-pulegone (5), which is subsequently shown to be a substrate for NtDBR (Nicotiana tabacum double-bond reductase) to afford (-)-menthone (7) and (+)-isomenthone (8).
A mechanistic investigation of alkene epoxidation by sterically encumbered trans-dioxoruthenium(VI) porphyrins
Liu, Chun-Jin,Yu, Wing-Yiu,Che, Chi-Ming,Yeung, Chi-Hung
, p. 7365 - 7374 (2007/10/03)
The highly substituted dioxoruthenium(VI) porphyrins [Ru(VI)(DPP)O2] (1a; H2DPP = 2,3,5,7,8,10,12,13,15,17,18,20-dodecaphenylporphyrin), [Ru(VI)(TDCPP)O2] (1b; H2TDCPP = meso-tetrakis(2,6- dichlorophenyl)porphyrin), and [Ru(VI)(TMOPP)O2] (1c; H2TMOPP = meso- tetrakis(2,4,6-trimethoxyphenyl)porphyrin) are competent oxidants for alkene epoxidation. The oxidations were carried out in a CH2Cl2/Hpz solution, and a paramagnetic bis(pyrazolato)ruthenium(IV) porphyrin, [Ru(IV)(Por)(pz)2] (2; H2Por = H2DPP, H2TDCPP, H2TMOPP), was isolated and characterized. For the oxidation of cis-alkenes, stereoselectivity is dependent upon both the alkenes and the ruthenium oxidants, and it decreases in the order: cis- stilbene > cis-β-methylstyrene > cis-β-deuteriostyrene. The observation of inverse secondary KIE for the oxidation of β-d2-styrene [k(H)/k(D) = 0.87 (1a); 0.86 (1b)] but not for the α-deuteriostyrene oxidations suggests that the C-O bond formation is more advanced at the C(β) atom than at the C(α) atom of styrene, consistent with a nonconcerted mechanism. By consideration of spin delocalization and polar effects, the second-order rate constants for the oxidation of para-substituted styrenes by complexes 1a-c can linearly correlate with the carboradical substituent constants σ(mb) and σ(JJ)· (Jiang, X.-K. Acc. Chem. Res. 1997, 30, 283). This implies that the styrene oxidation by the dioxoruthenium(VI) porphyrins should involve rate-limiting generation of a benzylic radical intermediate, and the magnitude of |ρ·(JJ)/ρ(mb)| > 1 suggests that the spin delocalization effect is more important than the polar effect in the epoxidation reactions. The spontaneous epoxidation of trans-β-methylstyrene by the sterically encumbered [Ru(VI)(TDCPP)O2] and [Ru(VI)(TMOPP)O2] complexes and the comparable ΔS((+)) values for their reactions with trans-β-methylstyrene and styrene are incompatible with the 'side-on approach' model; a 'head-on approach' model is implicated.
