Peculiarities of promiscuous l-threonine transaldolases for enantioselective synthesis of β-hydroxy-α-amino acids

Hai Deng* (Corresponding Author), Shan Wang

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

4 Citations (Scopus)
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The introduction of β-hydroxy-α-amino acids (βHAAs) into organic molecules has received considerable attention as these molecules have often found widespread applications in bioorganic chemistry, medicinal chemistry and biomaterial science. Despite innovation of asymmetric synthesis of βHAAs, stereoselective synthesis to control the two chiral centres at C α and C β positions is still challenging, with poor atomic economy and multi protection and deprotection steps. These syntheses are often operated under harsh conditions. Therefore, a biotransformation approach using biocatalysts is needed to selectively introduce these two chiral centres into structurally diverse molecules. Yet, there are few ways that enable one-step synthesis of βHAAs. One is to extend the substrate scope of the existing enzyme inventory. Threonine aldolases have been explored to produce βHAAs. However, the enzymes have poor controlled installation at C β position, often resulting in a mixture of diastereoisomers which are difficult to be separated. In this respect, L-threonine transaldolases (LTTAs) offer an excellent potential as the enzymes often provide controlled stereochemistry at C α and C β positions. Another is to mine LTTA homologues and engineer the enzymes using directed evolution with the aim of finding engineered biocatalysts to accept broad substrates with enhanced conversion and stereoselectivity. Here, we review the development of LTTAs that incorporate various aldehyde acceptors to generate structurally diverse βHAAs and highlight areas for future developments. KEY POINTS: • The general mechanism of the transaldolation reaction catalysed by LTTAs • Recent advances in LTTAs from different biosynthetic pathways • Applications of LTTAs as biocatalysts for production of βHAAs.

Original languageEnglish
Pages (from-to)3507–3520
Number of pages14
JournalApplied Microbiology and Biotechnology
Early online date26 Apr 2021
Publication statusPublished - 1 May 2021

Bibliographical note

This study was funded by Biotechnology and Biological Sciences Research Council UK (BBSRC) (BB/P00380X/1, BB/R00479X/1 and BB/R50547X/1), Scottish Funding Council COVID-19 Grant extension and Bridging Fund, and Industrial Biotechnology Innovation Centre (IBioIC, Scotland).
open access via springer agreement


  • Biotechnology
  • Applied Microbiology and Biotechnology
  • General Medicine


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