Postsynthetic Modification of Bacterial Peptidoglycan Using Bioorthogonal N-Acetylcysteamine Analogs and Peptidoglycan O-Acetyltransferase B.
Postsynthetic Modification of Bacterial Peptidoglycan Using Bioorthogonal N-Acetylcysteamine Analogs and Peptidoglycan O-Acetyltransferase B.
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DOI：
10.1021/jacs.7b06820
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发表时间：
2017-10-04
影响因子：
15
通讯作者：
Grimes CL
中科院分区：
文献类型：
--
作者：
Wang Y;Lazor KM;DeMeester KE;Liang H;Heiss TK;Grimes CL
细菌具有天然的能力，可以在其细菌肽聚糖(PG)上安装保护性的合成后修饰，PG是编织到细菌细胞壁的外套。肽聚糖O-乙酰基转移酶B(PatB)催化革兰氏(-)细菌中PG的O-乙酰化，这有助于细菌的生存，因为它阻止自溶酶(如溶菌酶)切割PG。我们探索了PatB乙酰化功能的机制细节，并确定PatB对生物正交短N-乙酰半胱胺(SNAC)供体具有底物专一性。一种PG模拟物三-N-乙酰氨基葡萄糖(NAG)3以及从各种革兰氏(+)和革兰氏(-)细菌中分离出来的PG上安装了包括叠氮化物和炔烃在内的各种功能。生物正交修饰可保护分离的PG不受溶菌酶的体外降解。我们进一步证明，这种PG的合成后修饰可以扩展到使用点击化学来荧光标记整个枯草杆菌细菌细胞中的成熟PG。通过扩大对PG如何被裂解酶处理的理解，对PG进行后合成修饰可以帮助开发抗生素和免疫调节剂。
Bacteria have the natural ability to install protective post-synthetic 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)3, 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 post-synthetic 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 post-synthetically can aid in the development of antibiotics and immune modulators by expanding the understanding of how PG is processed by lytic enzymes.
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DOI：
10.1002/anie.201206749
发表时间：
2012-12-07
期刊：
Angewandte Chemie (International ed. in English)
影响因子：
--
作者：
Kuru E;Hughes HV;Brown PJ;Hall E;Tekkam S;Cava F;de Pedro MA;Brun YV;VanNieuwenhze MS
通讯作者：
VanNieuwenhze MS
影响因子：
3.6
作者：
Bera, A;Herbert, S;Götz, F
通讯作者：
Götz, F
影响因子：
3.2
作者：
BLUNDELL, JK;PERKINS, HR
通讯作者：
PERKINS, HR
影响因子：
16.6
作者：
Liang H;DeMeester KE;Hou CW;Parent MA;Caplan JL;Grimes CL
通讯作者：
Grimes CL
影响因子：
2.9
作者：
Moynihan, Patrick J.;Clarke, Anthony J.
通讯作者：
Clarke, Anthony J.