Novel (S)-Selective Hydrolase from Arthrobacter sp. K5 for Kinetic Resolution of Cyclic Amines

Yuta Fukawa,Keisuke Kawade,Yuta Mizuno,Koichi Mitsukura,Toyokazu Yoshida

doi:10.3390/catal11070809

Abstract

Chiral 2-methylpiperidine (2-MPI) is an important building block that has potential for applications in pharmaceuticals and pesticides. In this study, we observed that the hydrolase in Arthrobacter sp. K5 exhibits high (S)-selectivity toward rac-N-pivaloyl-2-MPI to yield (S)-2-MPI with 80.2% enantiomeric excess (ee) in a 38.2% conversion. The hydrolase, which was identified by analyses of partial amino acid sequences of the purified enzyme and genome sequence of Arthrobacter sp. K5, exhibited moderate homology with amidohydrolases up to 67% (molinate hydrolase from Gulosibacter molinativorax). The hydrolase gene was overexpressed in Rhodococcus erythropolis. The recombinant cells produced (S)-2-MPI with 83.5% ee in a 48.4% conversion (E = 26.3) from 100 mM rac-N-pivaloyl-2-MPI. These results suggest the possibility of an efficient preparation of chiral 2-MPI in kinetic resolution.

Highlights

Of 10 with regard to jurisdictional claims in can be commercially available as inexpensive raw materials, in this study, we focused on published maps and institutional affilstereoselective hydrolases for 2-MPI production
Active amines can be prepared from racemic amine by diastereomeric salt formation using chiral carboxylic acids [17] or by stereoselective bioconversion of racemic
We predicted that the acyl group selectivity kinetically, yielding racemic 2-MPI (Figure 2a)

Summary

Introduction

The hydrolase gene was overexpressed in Rhodococcus erythropolis. The recombinant cells produced (S)-2-MPI with 83.5% ee in a 48.4% conversion (E = 26.3) from 100 mM rac-N-pivaloyl-2-MPI. These results suggest the possibility of an efficient preparation of chiral 2-MPI in kinetic resolution. In the synthesis of SS220, (S)-2-MPI moiety makes it effective or more effective than the most widely used insect repellent, N,N-diethyl-m-toluamide (DEET) [10,11,12]. The. Catalysts 2021, 11, x FOR PEER REVIEW of 10 with regard to jurisdictional claims in can be commercially available as inexpensive raw materials, in this study, we focused on published maps and institutional affilstereoselective hydrolases for 2-MPI production.

Methods

Results

Conclusion