Amide N-glycosylation by Asm25, an N-glycosyltransferase of ansamitocins
Zhao, Peiji2; Bai, Linquan1; Ma, Juan2; Zeng, Ying2; Li, Lei1; Zhang, Yirong1; Lu, Chunhua3; Dai, Huanqin2; Wu, Zhaoxian3; Li, Yaoyao3; Wu, Xuan3; Chen, Gang2; Hao, Xiaojiang2; Shen, Yuemao2,3; Deng, Zixin1; Floss, Heinz G.4
2008-08-25
发表期刊CHEMISTRY & BIOLOGY
ISSN1074-5521
卷号15期号:8页码:863-874
摘要Ansamitocins are potent antitumor maytansinoids produced by Actinosynnema pretiosum. Their biosynthesis involves the initial assembly of a macrolactam polyketide, followed by a series of postpolyketide synthase (PKS) modifications. Three ansamitocin glycosides were isolated from A. pretiosum and fully characterized structurally as novel ansamitocin derivatives, carrying a (3-D-glucosyl group attached to the macrolactam amide nitrogen in place of the N-methyl group. By gene inactivation and complementation, asm25 was identified as the N-glycosyltransferase gene responsible for the macrolactam amide N-glycosylation of ansamitocins. Soluble, enzymatically active Asm25 protein was obtained from asm25-expressing E, coli by solubilization from inclusion bodies. Its optimal reaction conditions, including temperature, pH, metal ion requirement, and Km/Kcat, were determined. Asm25 also showed broad substrate specificity toward other ansamycins and synthetic indolin-2-ones. To the best of our knowledge, this represents the first in vitro characterization of a purified antibiotic N-glycosyltransferase.
关键词Biosynthetic Gene-cluster Lechevalieria-aerocolonigenes Atcc-39243 Escherichia-coli 3-amino-5-hydroxybenzoic Acid Actinosynnema-pretiosum Maytansinoid Antibiotics Streptomyces Sp Indolocarbazole Expression Substrate
学科领域Biochemistry & Molecular Biology
DOI10.1016/j.chembiol.2008.06.007
收录类别SCI
语种英语
WOS记录号WOS:000258940000014
引用统计
文献类型期刊论文
条目标识符http://ir.kib.ac.cn/handle/151853/1707
专题植物化学与西部植物资源持续利用国家重点实验室
作者单位1.Shanghai Jiao Tong Univ, Coll Life Sci & Biotechnol, Lab Microbial Metab, Shanghai 200240, Peoples R China
2.Chinese Acad Sci, Kunming Inst Bot, State Key Lab Phytochem & Plant Resources W China, Kunming 650204, Yunnan, Peoples R China
3.Xiamen Univ, Key Lab Minist Educ Cell Biol & Tumor Cell Engn, Sch Life Sci, Fujian 361005, Peoples R China
4.Univ Washington, Dept Chem, Seattle, WA 98195 USA
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Zhao, Peiji,Bai, Linquan,Ma, Juan,et al. Amide N-glycosylation by Asm25, an N-glycosyltransferase of ansamitocins[J]. CHEMISTRY & BIOLOGY,2008,15(8):863-874.
APA Zhao, Peiji.,Bai, Linquan.,Ma, Juan.,Zeng, Ying.,Li, Lei.,...&Floss, Heinz G..(2008).Amide N-glycosylation by Asm25, an N-glycosyltransferase of ansamitocins.CHEMISTRY & BIOLOGY,15(8),863-874.
MLA Zhao, Peiji,et al."Amide N-glycosylation by Asm25, an N-glycosyltransferase of ansamitocins".CHEMISTRY & BIOLOGY 15.8(2008):863-874.
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