title: Expanding the Imine Reductase Toolbox by Exploring the Bacterial Protein-Sequence Space.
abstract: Recent investigations on imine reductases (IREDs) have enriched the toolbox of potential catalysts for accessing chiral amines, which are important building blocks for the pharmaceutical industry. Herein, we describe the characterization of 20 new IREDs. A C-terminal domain clustering of the bacterial protein-sequence space was performed to identify the novel IRED candidates. Each of the identified enzymes was characterized against a set of nine cyclic imine model substrates. A refined clustering towards putative active-site residues was performed and was consistent both with our screening and previously reported results. Finally, preparative scale experiments on a 100 mg scale with two purified IREDs, IR_20 from Streptomyces tsukubaensis and IR_23 from Streptomyces vidiochromogenes, were carried out to provide (R)-2-methylpiperidine in 98% ee (71% yield) and (R)-1-methyl-1,2,3,4-tetrahydroisoquinoline in >98% ee (82% yield).
authors.affiliation: Process Research and Development, F. Hoffmann-La Roche Ltd. Grenzacherstrasse 124, 4070 Basel (Switzerland).
authors.forename: Dennis
authors.initials: D
authors.lastname: Wetzl
authors.affiliation: Process Research and Development, F. Hoffmann-La Roche Ltd. Grenzacherstrasse 124, 4070 Basel (Switzerland).|Pharmaceutical Research and Early Development, F. Hoffmann-La Roche Ltd. Grenzacherstrasse 124, 4070 Basel (Switzerland).
authors.forename: Marco
authors.initials: M
authors.lastname: Berrera
authors.affiliation: Process Research and Development, F. Hoffmann-La Roche Ltd. Grenzacherstrasse 124, 4070 Basel (Switzerland).
authors.forename: Nicolas
authors.initials: N
authors.lastname: Sandon
authors.affiliation: Process Research and Development, F. Hoffmann-La Roche Ltd. Grenzacherstrasse 124, 4070 Basel (Switzerland).
authors.forename: Dan
authors.initials: D
authors.lastname: Fishlock
authors.affiliation: Process Research and Development, F. Hoffmann-La Roche Ltd. Grenzacherstrasse 124, 4070 Basel (Switzerland).|Pharmaceutical Research and Early Development, F. Hoffmann-La Roche Ltd. Grenzacherstrasse 124, 4070 Basel (Switzerland).
authors.forename: Martin
authors.initials: M
authors.lastname: Ebeling
authors.affiliation: Institute of Pharmaceutical Sciences, Albert-Ludwigs-Universität Freiburg, Albertstrasse 25, 79104 Freiburg (Germany).
authors.forename: Michael
authors.initials: M
authors.lastname: Müller
authors.affiliation: Process Research and Development, F. Hoffmann-La Roche Ltd. Grenzacherstrasse 124, 4070 Basel (Switzerland).
authors.forename: Steven
authors.initials: S
authors.lastname: Hanlon
authors.affiliation: Process Research and Development, F. Hoffmann-La Roche Ltd. Grenzacherstrasse 124, 4070 Basel (Switzerland).
authors.forename: Beat
authors.initials: B
authors.lastname: Wirz
authors.affiliation: Process Research and Development, F. Hoffmann-La Roche Ltd. Grenzacherstrasse 124, 4070 Basel (Switzerland). hans.iding@roche.com.
authors.forename: Hans
authors.initials: H
authors.lastname: Iding
mesh_terms: D001426:Bacterial Proteins / Q000737:chemistry / Q000235:genetics*; D020134:Catalytic Domain; D007097:Imines / Q000737:chemistry*; D008958:Models, Molecular; D015394:Molecular Structure; D010088:Oxidoreductases / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D054852:Small Molecule Libraries / Q000737:chemistry
chemical_list: D001426:Bacterial Proteins; D007097:Imines; D054852:Small Molecule Libraries; D010088:Oxidoreductases
keywords: asymmetric catalysis; biocatalysis; chiral amines; imine reductases; oxidoreductases