Efficient Stereoselective Synthesis of Structurally Diverse γ‐ and δ‐Lactones Using an Engineered Carbonyl Reductase

Abstract

Structurally diverse γ‐ and δ‐lactones were efficiently synthesized stereoselectively using an engineered carbonyl reductase from Serratia marcescens (SmCRV4). SmCRV4 exhibited improved activity (up to 500‐fold) and thermostability toward 14 γ‐/δ‐keto acids and esters, compared with the wild‐type enzyme, with 110‐fold enhancement in catalytic efficiency (kcat/Km) toward methyl 4‐oxodecanoate. The preparative synthesis of alkyl and aromatic γ‐ and δ‐lactones with 95 %–>99 % ee and 78 %–90 % yields was demonstrated. The highest space‐time yield, 1175 g L−1 d−1, was achieved for (R)‐γ‐decalactone.

The Synthesis of Chiral γ‐Lactones by Merging Decatungstate Photocatalysis with Biocatalysis

“…γ‐Lactones are important biologically active molecules and provide building blocks for various fine chemicals (Scheme 1a) [11–16] . Moreover, they are highly relevant structures both in the food and cosmetic industries as flavors and fragrances [24] . For instance, γ‐decalactone provides a characteristic aroma of peaches [19,24] …”

“…Moreover, they are highly relevant structures both in the food and cosmetic industries as flavors and fragrances [24] . For instance, γ‐decalactone provides a characteristic aroma of peaches [19,24] …”

Rational Design of Dehydrogenase/Reductases Based on Comparative Structural Analysis of Prereaction-State and Free-State Simulations for Efficient Asymmetric Reduction of Bulky Aryl Ketones

“…In our previous study, a short-chain dehydrogenase/reductase (SDR) from Empedobacter brevis ZJUY-1401 (EbSDR8, GenBank: ALZ42979.1) was discovered to be an excellent dehydrogenase/reductase for R-selective reduction of prochiral aryl ketones to the corresponding alcohols, , and its catalytic efficiency was further improved by G94A/S153L double mutations . However, Mu0 (EbSDR8-G94A/S153L) showed poor activity toward bulky aryl ketones such as o-halogenated acetophenones, propiophenones, aromatic ketoesters, and diaryl ketones that are highly demanded in pharmaceuticals, agricultural chemistry, fragrance, and fine chemical industries. ,,, In this study, the structural basis preventing the catalysis of 2′-bromoacetophenone ( 2a ) by Mu0 is revealed via enzyme–substrate docking and molecular dynamics (MD) simulations for T-state and F-state so as to identify the engineering targets.…”

“…8 However, Mu0 (EbSDR8-G94A/S153L) showed poor activity toward bulky aryl ketones such as ohalogenated acetophenones, propiophenones, aromatic ketoesters, and diaryl ketones that are highly demanded in pharmaceuticals, agricultural chemistry, fragrance, and fine chemical industries. 10,11,18,19 In this study, the structural basis preventing the catalysis of 2′-bromoacetophenone (2a) by Mu0 is revealed via enzyme−substrate docking and molecular dynamics (MD) simulations for T-state and F-state so as to identify the engineering targets.…”

Confining enzyme clusters in supramolecular nanoreactors enhances cofactor-dependent cascade for chiral alcohol synthesis

“…Cell-free cofactor recycling can be achieved by integrating an auxiliary enzyme which catalyzes a sacri cial and inexpensive substrate to regenerate cofactors. For example, NADPH can be recovered from NAD + using a glucose dehydrogenase and glucose [15][16][17][18][19][20] . Generally, the main and auxiliary enzymes are used as free enzymes in the reaction solution.…”