An unusual metal-bound 4-fluorothreonine transaldolase from Streptomyces sp. MA37 catalyses promiscuous transaldol reactions.


Journal

Applied microbiology and biotechnology
ISSN: 1432-0614
Titre abrégé: Appl Microbiol Biotechnol
Pays: Germany
ID NLM: 8406612

Informations de publication

Date de publication:
May 2020
Historique:
received: 11 09 2019
accepted: 23 02 2020
revised: 13 02 2020
pubmed: 7 3 2020
medline: 9 1 2021
entrez: 7 3 2020
Statut: ppublish

Résumé

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 Zn

Identifiants

pubmed: 32140842
doi: 10.1007/s00253-020-10497-z
pii: 10.1007/s00253-020-10497-z
pmc: PMC7162832
doi:

Substances chimiques

Amino Acids, Aromatic 0
Bacterial Proteins 0
4-fluorothreonine 102130-93-8
Threonine 2ZD004190S
Transaldolase EC 2.2.1.2
Zinc J41CSQ7QDS

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

3885-3896

Subventions

Organisme : National Outstanding Youth Science Fund Project of National Natural Science Foundation of China
ID : 31570033, 31811530299, and 31870035
Organisme : Biotechnology and Biological Sciences Research Council
ID : BB/P00380X/1
Pays : United Kingdom
Organisme : Leverhulme Trust
ID : RPG-2014-418
Organisme : Medical Research Council
ID : MR/S00520X/1
Pays : United Kingdom
Organisme : Royal Asiatic Society of Great Britain and Ireland
ID : IEC\NSFC\170617
Organisme : Leverhulme Trust
ID : AA090088

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Auteurs

Linrui Wu (L)

Department of Chemistry, University of Aberdeen, Aberdeen, AB24 3UE, UK.

Ming Him Tong (MH)

Department of Chemistry, University of Aberdeen, Aberdeen, AB24 3UE, UK.

Andrea Raab (A)

Department of Chemistry, University of Aberdeen, Aberdeen, AB24 3UE, UK.

Qing Fang (Q)

Department of Chemistry, University of Aberdeen, Aberdeen, AB24 3UE, UK.

Shan Wang (S)

Department of Chemistry, University of Aberdeen, Aberdeen, AB24 3UE, UK.

Kwaku Kyeremeh (K)

Department of Chemistry, University of Ghana, P.O. Box LG56, Legon-Accra, Ghana.

Yi Yu (Y)

Key Laboratory of Combinatorial Biosynthesis and Drug Discovery (MOE) and Hubei Province Engineering and Technology Research Centre for Fluorinated Pharmaceuticals, School of Pharmaceutical Sciences, Wuhan University, Wuhan, 430071, China.

Hai Deng (H)

Department of Chemistry, University of Aberdeen, Aberdeen, AB24 3UE, UK. h.deng@abdn.ac.uk.

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