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Engineering the Active Site of the Amine Transaminase from Vibrio fluvialis for the Asymmetric Synthesis of Aryl–Alkyl Amines and Amino Alcohols
Author(s) -
Nobili Alberto,
SteffenMunsberg Fabian,
Kohls Hannes,
Trentin Ivan,
Schulzke Carola,
Höhne Matthias,
Bornscheuer Uwe T.
Publication year - 2015
Publication title -
chemcatchem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.497
H-Index - 106
eISSN - 1867-3899
pISSN - 1867-3880
DOI - 10.1002/cctc.201403010
Subject(s) - chemistry , aryl , alkyl , transamination , amine gas treating , substituent , enantiomeric excess , organic chemistry , biocatalysis , catalysis , combinatorial chemistry , enantioselective synthesis , enzyme , reaction mechanism
Although the amine transaminase from Vibrio fluvialis has often been applied as a catalyst for the biocatalytic preparation of various chiral primary amines, it is not suitable for the transamination of α‐hydroxy ketones and aryl‐alkyl ketones bearing an alkyl substituent larger than a methyl group. We addressed this problem through a systematic mutagenesis study of active site residues to expand its substrate scope towards two bulky ketones. We identified two mutants (F85L/V153A and Y150F/V153A) showing 30‐fold increased activity in the conversion of ( S )‐phenylbutylamine and ( R )‐phenylglycinol, respectively. Notably, they facilitated asymmetric synthesis of these amines with excellent enantiomeric purities of 98 % ee .