The application of ketoreductase-based biocatalytic reduction to access optically pure Prelog or anti-Prelog alcohols offers a valuable approach for asymmetric synthesis. Despite this, control of the stereopreferences of ketoreductases as desired remains challenging, since natural ketoreductases usually display Prelog preference and it is difficult to transfer the knowledge from engineered anti-Prelog ketoreductases to the others. Here, we present the discovery of a switch between Prelog and anti-Prelog reduction toward halogen-substituted acetophenones in six short-chain dehydrogenase/reductases (SDRs). Through carefully analysis of the structural information and multiple-sequence alignment of several reported SDRs with Prelog or anti-Prelog stereopreference, the key residues that might control their stereopreferences were identified using Lactobacillus fermentum short-chain dehydrogenase/reductase 1 (LfSDR1) as the starting enzyme. Protein engineering at these positions of LfSDR1 could improve its anti-Prelog stereoselectivity or switch its stereopreference to Prelog. Moreover, the knowledge obtained from LfSDR1 could be further transferred to the five other SDRs (four mined SDRs and one reported SDR) that have 21−48% sequence identities with LfSDR1. The stereopreferences of these SDRs were able to be switched either from anti-Prelog to Prelog or from Prelog to anti-Prelog by mutagenesis at related positions. In addition, further optimization of LfSDR1 can access stereocomplementary reduction of several halogen-substituted acetophenones with high stereoselectivity (up to >99%), resulting in some valuable chiral alcohols for the synthesis of pharmaceutical agents.
Chiral carveol and dihydrocarveol are important additives in the flavor industry and building blocks in the synthesis of natural products. Despite the remarkable progress in asymmetric catalysis, convenient access to all possible stereoisomers of carveol and dihydrocarveol remains a challenge. Here, we present the stereodivergent synthesis of carveol and dihydrocarveol through ketoreductases/ene‐reductases catalyzed asymmetric reduction. By directly asymmetric reduction of (R)‐ and (S)‐carvone using ketoreductases, which have Prelog or anti‐Prelog stereopreference, all four possible stereoisomers of carveol with medium to high diastereomeric excesses (up to >99 %) were first observed. Then four stereoisomers of dihydrocarvone were prepared through ene‐reductases catalyzed diastereoselective synthesis. Asymmetric reduction of obtained dihydrocarvone isomers by ketoreductases further provide access to all eight stereoisomeric dihydrocarveol with up to 95 % de values. In addition, the absolute configurations of dihydrocarveol stereoisomers were determined by using modified Mosher's method.
With the advantages of light absorption ability, photo-stability and moisture resistance, triple cation perovskites (TCPs) have great application prospects in optoelectronic devices. Here, we reveal a novel inverse photoconductivity (IPC)...
Ketoreductase (KRED)-catalyzed asymmetric reduction of prochiral ketones is an attractive method to synthesize chiral alcohols. Herein, two KREDs LfSDR1-V186A/E141I and CgKR1-F92I with complementary stereopreference were identified towards reduction of apremilast...
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