An L-threonine aldolase for asymmetric synthesis of β-hydroxy-α-amino acids

Abstract

L-threonine aldolase (LTA) is a PLP-dependent enzyme that can reversibly catalyze aldol reaction of glycine and acetaldehyde to produce β-hydroxy-α-amino acids. In the present work, a putative lta gene from Actinocorallia herbida (AhLTA) was mined and over-expressed in Escherichia coli BL21 (DE3). The substrate spectrum assay indicated that AhLTA only used glycine as donor substrate and tolerated a wild range of aromatic aldehydes as acceptor substrates. It was found that the type and position of substituents in the aromatic aldehydes exerted a significant impact on the activity and stereoselectivity at β-carbon of AhLTA. Among those substrates, AhLTA could catalyze glycine and 4-methylsulphonyl benzaldehyde (14a) to produce L-threo-4-methylsulfonylphenylserine ((2S,3R)-14b) with high conversion (94.4%) and moderate stereoselectivity (19% de). By conditional optimization, the de value of (2S, 3R)-14b was improved to 61% and the conversion was 75%. Taken together, our study suggested that AhLTA might be a promising catalyst for producing chiral β-hydroxy-α-amino acids.