Flack, E.K.P., Chidwick, H.S., Guchhait, G. et al. (13 more authors) (2020) Biocatalytic transfer of pseudaminic acid (Pse5Ac7Ac) using promiscuous sialyltransferases in a chemoenzymatic approach to Pse5Ac7Ac-containing glycosides. ACS Catalysis, 10. pp. 9986-9993. ISSN 2155-5435
Abstract
Pseudaminic acid (Pse5Ac7Ac) is a nonmammalian sugar present on the cell surface of a number of bacteria including Pseudomonas aeruginosa, Campylobacter jejuni, and Acinetobacter baumannii. However, the role Pse5Ac7Ac plays in host–pathogen interactions remains underexplored, particularly compared to its ubiquitous sialic acid analogue Neu5Ac. This is primarily due to a lack of access to difficult to prepare Pse5Ac7Ac glycosides. Herein, we describe the in vitro biocatalytic transfer of an activated Pse5Ac7Ac donor onto glycosyl acceptors, enabling the enzymatic synthesis of Pse5Ac7Ac-containing glycosides. In a chemoenzymatic approach, chemical synthesis initially afforded access to a late-stage Pse5Ac7Ac biosynthetic intermediate, which was subsequently converted to the desired CMP-glycosyl donor in a one-pot two-enzyme process using biosynthetic enzymes. Finally, screening a library of 13 sialyltransferases (SiaT) with the unnatural substrate enabled the identification of a promiscuous inverting SiaT capable of turnover to afford β-Pse5Ac7Ac-terminated glycosides.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2020 American Chemical Society. This is an author-produced version of a paper subsequently published in ACS Catalysis. Uploaded in accordance with the publisher's self-archiving policy. |
Keywords: | chemoenzymatic synthesis; pseudaminic acid glycosides; sialyltransferases; sialic acid mimics; biocatalysis |
Dates: |
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Institution: | The University of Sheffield |
Academic Units: | The University of Sheffield > Sheffield Teaching Hospitals |
Depositing User: | Symplectic Sheffield |
Date Deposited: | 27 Aug 2020 10:35 |
Last Modified: | 21 Aug 2021 00:38 |
Status: | Published |
Publisher: | American Chemical Society (ACS) |
Refereed: | Yes |
Identification Number: | 10.1021/acscatal.0c02189 |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:164868 |