An unusual metal-bound 4-fluorothreonine transaldolase from Streptomyces sp. MA37 catalyses promiscuous transaldol reactions
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Date
2020-03-06
Journal Title
Journal ISSN
Volume Title
Publisher
Applied Microbiology and Biotechnology
Abstract
β-Hydroxy-α-amino acids (βH-AAs) are key components of many bioactive molecules as well as exist as specialised metabolites.
Among these βH-AAs, 4-fluorothreonine (4-FT) is the only naturally occurring fluorinated AA discovered thus far. Here
we report overexpression and biochemical characterisation of 4-fluorothreonine transaldolase from Streptomyces sp. MA37
(FTaseMA), a homologue of FTase previously identified in the biosynthesis of 4-FT in S. cattleya. FTaseMA displays considerable
substrate plasticity to generate 4-FT as well as other β-hydroxy-α-amino acids with various functionalities at C4 position,
giving the prospect of new chemo-enzymatic applications. The enzyme has a hybrid of two catalytic domains, serine
hydroxymethyltransferase (S) and aldolase (A). Site-directed mutagenesis allowed the identification of the key residues of
FTases, suggesting that the active site of A domain has a historical reminiscent feature in metal-dependent aldolases.
Elemental analysis demonstrated that FTaseMA is indeed a Zn2+-dependent enzyme, the first example of pyridoxal phosphate
(PLP) enzyme family fused with a metal-binding domain carrying out a distinct catalytic role. Finally, FTaseMA showed
divergent evolutionary origin with other PLP dependent enzymes
Description
Research Article
Keywords
β-Hydroxy-α-amino acids, 4-fluorothreonine, 4-fluorothreonine transaldolase, Transaldolation, Streptomyces sp., MA37
Citation
Wu, L., Tong, M.H., Raab, A. et al. An unusual metal-bound 4-fluorothreonine transaldolase from Streptomyces sp. MA37 catalyses promiscuous transaldol reactions. Appl Microbiol Biotechnol 104, 3885–3896 (2020). https://doi.org/10.1007/s00253-020-10497-z