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Improving the Cβ Stereoselectivity of l‐Threonine Aldolase for the Synthesis of l‐threo‐4‐Methylsulfonylphenylserine by Modulating the Substrate‐Binding Pocket To Control the Orientation of the Substrate Entrance
- Source :
-
Chemistry - A European Journal . 7/2/2021, Vol. 27 Issue 37, p9654-9660. 7p. - Publication Year :
- 2021
-
Abstract
- l‐Threonine aldolase from Actinocorallia herbida (AhLTA) is an ideal catalyst for producing l‐threo‐4‐methylsulfonylphenylserine [(2S,3R)‐1 b], a key chiral precursor for florfenicol and thiamphenicol. The moderate Cβ stereoselectivity is the main obstacle to the industrial application of AhLTA. To address this issue, a combinatorial active‐site saturation test (CAST) together with sequence conservatism analysis was applied to engineer the AhLTA toward improved Cβ stereoselectivity. The optical mutant Y314R could asymmetrically synthesize l‐threo‐4‐methylsulfonylphenylserine with 81 % diastereomeric excess (de), which is 23 % higher than wild‐type AhLTA. Molecular dynamic (MD) simulations revealed that the mechanism for the improvement in Cβ stereoselectivity of Y314R is due to the acylamino group of residues Arg314 controlling the orientation of substrate 4‐methylsulfonyl benzaldehyde (1 a) in the active pocket by directed interaction with the methylsulfonyl group; this leads to asymmetric synthesis of l‐threo‐4‐methylsulfonylphenylserine. The success in this study demonstrates that direct control of substrates in an active pocket is an attract strategy to address the Cβ stereoselectivity problem of LTA and contribute to the industrial application of LTA. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 09476539
- Volume :
- 27
- Issue :
- 37
- Database :
- Academic Search Index
- Journal :
- Chemistry - A European Journal
- Publication Type :
- Academic Journal
- Accession number :
- 151211887
- Full Text :
- https://doi.org/10.1002/chem.202100752