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利用形成N-P键的激酶对脱氧糖氨基磷酸酯金属蛋白酶抑制剂进行生物合成重构。

Biosynthetic reconstitution of deoxysugar phosphoramidate metalloprotease inhibitors using an N-P-bond-forming kinase.

作者信息

Baulig Alexandra, Helmle Irina, Bader Marius, Wolf Felix, Kulik Andreas, Al-Dilaimi Arwa, Wibberg Daniel, Kalinowski Jörn, Gross Harald, Kaysser Leonard

机构信息

Department of Pharmaceutical Biology , Pharmaceutical Institute , University of Tübingen , 72076 Tübingen , Germany . Email:

German Centre for Infection Research (DZIF) , partner site Tübingen , 72076 Tübingen , Germany.

出版信息

Chem Sci. 2019 Mar 21;10(16):4486-4490. doi: 10.1039/c9sc00641a. eCollection 2019 Apr 28.

DOI:10.1039/c9sc00641a
PMID:31057776
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6482885/
Abstract

Phosphoramidon is a potent metalloprotease inhibitor and a widespread tool in cell biology research. It contains a dipeptide backbone that is uniquely linked to a 6-deoxysugar a phosphoramidate bridge. Herein, we report the identification of a gene cluster for the formation of phosphoramidon and its detailed characterization. reconstitution of the biosynthesis established TalE as a phosphoramidate-forming kinase and TalC as the glycosyltransferase which installs the l-rhamnose moiety by phosphoester linkage.

摘要

磷酰胺脒是一种有效的金属蛋白酶抑制剂,也是细胞生物学研究中广泛使用的工具。它含有一个二肽主链,该主链通过一个磷酰胺桥与一个6-脱氧糖独特相连。在此,我们报告了磷酰胺脒形成基因簇的鉴定及其详细表征。生物合成的重建确定TalE为形成磷酰胺的激酶,TalC为糖基转移酶,其通过磷酸酯键安装L-鼠李糖部分。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f289/6482885/2d86bcc70bb3/c9sc00641a-f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f289/6482885/a0be67391945/c9sc00641a-f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f289/6482885/752e0be9796b/c9sc00641a-f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f289/6482885/fe8945f71a33/c9sc00641a-f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f289/6482885/2d86bcc70bb3/c9sc00641a-f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f289/6482885/a0be67391945/c9sc00641a-f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f289/6482885/752e0be9796b/c9sc00641a-f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f289/6482885/fe8945f71a33/c9sc00641a-f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f289/6482885/2d86bcc70bb3/c9sc00641a-f4.jpg

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