Biocatalytic Epoxidation for Green Synthesis

Production of Enantiopure Chiral Epoxides with E. coli Expressing Styrene Monooxygenase

“…From the group of unsaturated aldehydes and ketones, only 3b was transformed to epoxide with excellent enantiopurity (ee ˃ 99%). Interestingly, 3b only differs from 3a by one methyl- substitution on C 2 carbon, which supports the previous finding of SMO activity enhancement by double bond methylation [ 14 ]. On the other hand, no activity towards 4c was observed, suggesting that the combination of methyl- and carbonyl- substituents was crucial.…”

“…Initially, SMOs were considered as enzymes with a narrow substrate spectrum, especially those originating from Pseudomonas and Rhodococcus species. However, recent studies described novel SMOs from various bacteria or metagenome, which provided novel insights into the catalytic mechanism of styrene epoxidation and, thereby, enabled the generation of SMOs with improved biocatalytic activities and a broader substrate spectrum [ 4 , 6 , 14 , 30 ]. So far, all studies have confirmed that few structural characteristics of the substrate significantly impact the biocatalysis: acyclic double bonds are preferred; an electron-withdrawing group conjugated to a double bond, α-/β-substitution of styrene/styrene derivatives, as well as 2-substitution of an aromatic ring decrease activity [ 5 , 6 , 12 , 13 , 31 ].…”

“…However, only a low cell concentration (12 g/L) was reached during fermentation, despite being operated on a pilot-scale [ 11 ]. Although recombinant production of SMO has been known for several decades, the majority of biotransformations are performed using whole-cell SMO that may cause a decline in enantiomeric excess (ee) of chiral products because of possible side reactions [ 2 , 12 , 13 , 14 ]. Few attempts of SMO isolation have been reported, but only the small-scale expression of StyA and StyB separately was successful [ 4 , 15 , 16 ].…”

“…However, biocatalysis still suffers from the low availability of enzymes in large quantities and is often replaced by chemical catalysis on an industrial scale. Sharpless and Jacobsen oxidation that demand extreme reaction conditions and suffer from poor enantioselectivity are mostly employed in pilot-scale chiral epoxides preparation [ 14 , 17 ]. Further improvement of SMO production (e.g., fermentation optimisation, enzyme stability improvement, effective purification development) significantly improves the production cost and enantiopurity of chiral epoxides.…”

A Unique P450 Peroxygenase System Facilitated by a Dual-Functional Small Molecule: Concept, Application, and Perspective

“…Asymmetric epoxidation of unfunctionalized olefins represents an important organic transformation to prepare optically pure epoxides [96][97][98][99]; however, the (R)-enantioselective epoxidation of styrene seems more difficult to achieve than the (S)-enantioselective reaction through either synthetic molecular catalysts or natural enzymatic bio-catalysts [100][101][102][103][104][105][106][107][108]. DFSM-facilitated P450BM3 peroxygenase enabled access to (R)-enantioselective epoxidation of unfunctionalized styrene and its derivatives (Figure 5).…”