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J Appl Microbiol ; 124(5): 1107-1121, 2018 May.
Article in English | MEDLINE | ID: mdl-29292556

ABSTRACT

AIMS: To screen 20 micro-organisms for ω-transaminase (ω-TA) activity by the kinetic resolution of rac-1-phenylethylamine, followed by testing rac-amines of pharmaceutical interest with bulky substituents and to conduct the asymmetric synthesis of a chiral amine. METHODS AND RESULTS: Stemphylium lycopersici was selected as the best biocatalyst. By the central composite rotatable design (CCRD), it was found that, at lower pH (5·5 and 6·5), the lyophilized micro-organism biocatalysed the kinetic resolution of rac-1-phenylethylamine with 99% enantiomeric excess (e.e.) ((R)-enantiomer) with acetophenone conversions ranged from 41 to 45%. Interestingly, the lyophilized crude enzymatic extract lead to better results at pH from 7·0 to 9·0, with conversions up to 47% and about 99% e.e. We also attested that as much as higher is the pyruvate (amino acceptor) concentration, higher is the acetophenone conversion, corroborating the presence of ω-TA-type enzymes. Among different sterically hindered racemic amines tested, rac-1,2,3,4-tetrahydro-1-naphthylamine and rac-phenylbutylamine were satisfactorily kinetically resolved in up to 91% e.e. (R). The results for the asymmetric synthesis showed excellent conversion (>85%) for the S-1-phenylethylamine, indicating (S)-stereopreference. CONCLUSION: Stemphylium lycopersici showed to be an important tool for broader substrate scope transaminases and a relevant player on the development of new biocatalysts with ability in asymmetric synthesis reactions. SIGNIFICANCE AND IMPACT OF THE STUDY: Here in, we contribute to the improvement of the biocatalytic toolbox for chiral amines synthesis. Interestingly, we have found that the crude enzymatic extract of the endophytic fungus S. lycopersici could accept bulky substrates with reasonable activity, compared to the wild-type transaminase already published over literature, and with high enantioselectivity.


Subject(s)
Amines/chemistry , Amines/metabolism , Ascomycota/enzymology , Acetophenones/metabolism , Biocatalysis , Biotransformation , Kinetics , Phenethylamines/chemistry , Phenethylamines/metabolism , Stereoisomerism , Transaminases/metabolism
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