Deciphering the sugar biosynthetic pathway and tailoring steps of nucleoside antibiotic A201A unveils a GDP-L-galactose mutase
文献类型：期刊论文
| 作者 | Zhu, QH; Chen, Q; Song, YX; Huang, HB; Li, J; Ma, JY; Li, QL; Ju, JH |
| 刊名 | PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
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| 出版日期 | 2017 |
| 卷号 | 114期号:19页码:4948-4953 |
| 关键词 | nucleoside antibiotic A201A biosynthesis GDP-L-galactose mutase methyltransferase desaturase |
| 通讯作者 | jju@scsio.ac.cn |
| 中文摘要 | Galactose, a monosaccharide capable of assuming two possible configurational isomers (D-/L-), can exist as a six-membered ring, galactopyranose (Galp), or as a five-membered ring, galactofuranose (Galf). UDP-galactopyranose mutase (UGM) mediates the conversion of pyranose to furanose thereby providing a precursor for D-Galf. Moreover, UGM is critical to the virulence of numerous eukaryotic and prokaryotic human pathogens and thus represents an excellent antimicrobial drug target. However, the biosynthetic mechanism and relevant enzymes that drive L-Galf production have not yet been characterized. Herein we report that efforts to decipher the sugar biosynthetic pathway and tailoring steps en route to nucleoside antibiotic A201A led to the discovery of a GDP-L-galactose mutase, MtdL. Systematic inactivation of 18 of the 33 biosynthetic genes in the A201A cluster and elucidation of 10 congeners, coupled with feeding and in vitro biochemical experiments, enabled us to: (i) decipher the unique enzyme, GDP-Lgalactose mutase associated with production of two unique D-mannose-derived sugars, and (ii) assign two glycosyltransferases, four methyltransferases, and one desaturase that regiospecifically tailor the A201A scaffold and display relaxed substrate specificities. Taken together, these data provide important insight into the origin of L-Galf-containing natural product biosynthetic pathways with likely ramifications in other organisms and possible antimicrobial drug targeting strategies. |
| 源URL | [http://ir.scsio.ac.cn/handle/344004/16284]  |
| 专题 | 南海海洋研究所_中科院海洋生物资源可持续利用重点实验室 |
| 推荐引用方式 GB/T 7714 | Zhu, QH,Chen, Q,Song, YX,et al. Deciphering the sugar biosynthetic pathway and tailoring steps of nucleoside antibiotic A201A unveils a GDP-L-galactose mutase[J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA,2017,114(19):4948-4953. |
| APA | Zhu, QH.,Chen, Q.,Song, YX.,Huang, HB.,Li, J.,...&Ju, JH.(2017).Deciphering the sugar biosynthetic pathway and tailoring steps of nucleoside antibiotic A201A unveils a GDP-L-galactose mutase.PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA,114(19),4948-4953. |
| MLA | Zhu, QH,et al."Deciphering the sugar biosynthetic pathway and tailoring steps of nucleoside antibiotic A201A unveils a GDP-L-galactose mutase".PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA 114.19(2017):4948-4953. |
入库方式： OAI收割
来源：南海海洋研究所
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