Exploring the Temperature Effect on Enantioselectivity of a Baeyer‐Villiger Biooxidation by the 2,5‐DKCMO Module: The SLM Approach

Abstract

Temperature is a crucial parameter for biological and chemical processes. Its effect on enzymatically catalysed reactions has been known for decades, and stereo-and enantiopreference are often temperature-dependent. For the first time, we present the temperature effect on the Baeyer-Villiger oxidation of racbicyclo[3.2.0]hept-2-en-6-one by the type II Bayer-Villiger monooxygenase, 2,5-DKCMO. In the absence of a reductase and driven by the hydride-donation of a synthetic nicotinamide analogue, the clear trend for a decreasing enantioselectivity at higher temperatures was observed. "Traditional" approaches such as the determination of the enantiomeric ratio (E) appeared unsuitable due to the complexity of the system. To quantify the trend, we chose to use the 'Shape Language Modelling' (SLM), a tool that allows the reaction to be described at all points in a shape prescriptive manner. Thus, without knowing the equation of the reaction, the substrate ee can be estimated that at any conversion.

Hybrid catalysis for enantioselective Baeyer–Villiger oxidation and stereoselective epoxidation: a Cp*Ir complex to fuel FMN and FAD reduction for flavoprotein monooxygenase modules

“…2,5-DKCMO accepts only a few number of substrates. 14,15 Among them, bicyclo[3.2.0]hept-2-en-6-one 2a , a well-known substrate of BVMOs, was chosen for its high activity against the enzyme in spite of moderate enantioselectivity and regioselectivity. Two regioisomeric lactones, called respectively “normal” and “abnormal” lactones, can be produced in various ratio as displayed Fig.…”

“…Its formation empowers the transition of two electrons from the hydride donor to the enzymatic part. Coupling the reactions, however, requires maintaining conditions favourable to both reactions, and also, as we previously demonstrated, 14,15 balancing the flavin reduction and oxidation rates to minimize the instability of the reduced flavin in the presence of dioxygen. Indeed, a reduction rate similar or lower than the oxidation rate must be favoured.…”

“…20 Substrate and products of 2,5-DKCMO biotransformation 2,5-DKCMO accepts only a few number of substrates. 14,15 Among them, bicyclo[3.2.0]hept-2-en-6-one 2a, a well-known substrate of BVMOs, was chosen for its high activity against the enzyme in spite of moderate enantioselectivity and regioselectivity.…”

“…Combining both previous concepts in a chemoenzymatic process, we applied an hybrid catalysis strategy to the oxidising module of 2,5-diketocamphanemonooxygenase I (2,5-DKCMO). [11][12][13][14][15] This enzyme is one of the two known representatives of the mechanistically intriguing family of type II BVMOs, belonging to the strictly FMN-dependent group C of FPMOs. 1,16,17 Due to its outstanding stability, 14,15 we combined the enzyme with the cyclopentadienyl type iridium complex 1-(H + ), 18 a pH-and O 2 -robust electron mediator, with conspicuous catalytic properties for the acetic acid hydrogenation.…”

“…[11][12][13][14][15] This enzyme is one of the two known representatives of the mechanistically intriguing family of type II BVMOs, belonging to the strictly FMN-dependent group C of FPMOs. 1,16,17 Due to its outstanding stability, 14,15 we combined the enzyme with the cyclopentadienyl type iridium complex 1-(H + ), 18 a pH-and O 2 -robust electron mediator, with conspicuous catalytic properties for the acetic acid hydrogenation. 19 Then, to expand the scope of 1-(H + ) for hybrid catalysis, we associated this catalyst with the highly stereoselective styrene monooxygenase, Sf StyA.…”