Deciphering the sugar biosynthetic pathway and tailoring steps of nucleoside antibiotic A201A unveils a GDP-L-galactose mutase
Zhu, QH; Chen, Q; Song, YX; Huang, HB; Li, J; Ma, JY; Li, QL; Ju, JH; jju@scsio.ac.cn
2017
发表期刊PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
卷号114期号:19页码:4948-4953
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.
部门归属[Zhu, Qinghua; Chen, Qi; Song, Yongxiang; Huang, Hongbo; Li, Jun; Ma, Junying; Li, Qinglian; Ju, Jianhua] Chinese Acad Sci, South China Sea Inst Oceanol, Res Network Appl Microbiol,Ctr Marine Microbiol, Guangdong Key Lab Marine Mat Med,Key Lab Trop Mar, Guangzhou 510301, Guangdong, Peoples R China; [Ju, Jianhua] Univ Chinese Acad Sci, Coll Earth Sci, Beijing 10049, Peoples R China
关键词Nucleoside Antibiotic A201a Biosynthesis Gdp-l-galactose Mutase Methyltransferase Desaturase
资助项目LMB
文献类型期刊论文
条目标识符http://ir.scsio.ac.cn/handle/344004/16284
专题中科院海洋生物资源可持续利用重点实验室
通讯作者jju@scsio.ac.cn
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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.,...&jju@scsio.ac.cn.(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.
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