Characterizing Amosamine Biosynthesis in Amicetin Reveals AmiG as a Reversible Retaining Glycosyltransferase

被引：26

作者：

Chen, Ruidong ^{[1
,2
]}

Zhang, Haibo ^{[1
]}

Zhang, Gaiyun ^{[3
]}

Li, Sumei ^{[1
]}

Zhang, Guangtao ^{[1
]}

Zhu, Yiguang ^{[1
]}

Liu, Jinsong ^{[4
]}

Zhang, Changsheng ^{[1
]}

机构：

[1] Chinese Acad Sci, South China Sea Inst Oceanol, Guangdong Key Lab Marine Mat Med, CAS Key Lab Trop Marine Bioresources & Ecol,RNAM, Guangzhou 510301, Guangdong, Peoples R China

[2] Chinese Acad Sci, Grad Univ, Beijing 100049, Peoples R China

[3] State Ocean Adm, Inst Oceanog 3, Key Lab Marine Biogenet Resources, Xiamen 361005, Peoples R China

[4] Chinese Acad Sci, Guangzhou Inst Biomed & Hlth, State Key Lab Resp Dis, Guangzhou 510530, Guangdong, Peoples R China

来源：

JOURNAL OF THE AMERICAN CHEMICAL SOCIETY | 2013年 / 135卷 / 33期

关键词：

IN-VITRO CHARACTERIZATION; GENE-CLUSTER; GLYCOSYLATION STEPS; ANTIBIOTICS; INSIGHTS;

D O I：

10.1021/ja401016e

中图分类号：

O6 [化学];

学科分类号：

0703 ;

摘要：

The antibacterial and antiviral agent amicetin is a disaccharide nucleoside antibiotic featuring a unique alpha-(1 -> 4)-glycoside bond between amosamine and amicetose, characteristic of a retaining glycosylation. In this study, two key steps for amosamine biosynthesis were investigated: the N-methyltransferase AmiH was demonstrated to be requisite for the dimethylation in amosamine, and the glycosyltransferase AmiG was shown to be necessary for amosaminylation. Biochemical and kinetic characterization of AmiG revealed for the first time the catalytic reversibility of a retaining glycosyltransferase involved in secondary metabolite biosynthesis. AmiG displayed substrate flexibility by utilizing five additional sugar nucleotides as surrogate donors. AmiG was also amenable to sugar and aglycon exchange reactions. This study indicates that AmiG is a potential catalyst for diversifying nucleoside antibiotics and paves the way for mechanistic studies of a natural-product retaining glycosyltransferase.

引用

页码：12152 / 12155

页数：4

共 29 条

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