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Postsynthetic Modification of Bacterial Peptidoglycan Using Bioorthogonal N-Acetylcysteamine Analogs and Peptidoglycan O-Acetyltransferase B.

Authors :
Wang Y
Lazor KM
DeMeester KE
Liang H
Heiss TK
Grimes CL
Source :
Journal of the American Chemical Society [J Am Chem Soc] 2017 Oct 04; Vol. 139 (39), pp. 13596-13599. Date of Electronic Publication: 2017 Sep 26.
Publication Year :
2017

Abstract

Bacteria have the natural ability to install protective postsynthetic modifications onto its bacterial peptidoglycan (PG), the coat woven into bacterial cell wall. Peptidoglycan O-acetyltransferase B (PatB) catalyzes the O-acetylation of PG in Gram (-) bacteria, which aids in bacterial survival, as it prevents autolysins such as lysozyme from cleaving the PG. We explored the mechanistic details of PatB's acetylation function and determined that PatB has substrate specificity for bioorthgonal short N-acetyl cysteamine (SNAc) donors. A variety of functionality including azides and alkynes were installed on tri-N-acetylglucosamine (NAG) <subscript>3</subscript> , a PG mimic, as well as PG isolated from various Gram (+) and Gram (-) bacterial species. The bioorthogonal modifications protect the isolated PG against lysozyme degradation in vitro. We further demonstrate that this postsynthetic modification of PG can be extended to use click chemistry to fluorescently label the mature PG in whole bacterial cells of Bacillus subtilis. Modifying PG postsynthetically can aid in the development of antibiotics and immune modulators by expanding the understanding of how PG is processed by lytic enzymes.

Details

Language :
English
ISSN :
1520-5126
Volume :
139
Issue :
39
Database :
MEDLINE
Journal :
Journal of the American Chemical Society
Publication Type :
Academic Journal
Accession number :
28898061
Full Text :
https://doi.org/10.1021/jacs.7b06820