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学科主题: 生命有机化学
题名: Metabolic coupling of two small-molecule thiols programs the biosynthesis of lincomycin A
其他题名: 两个小分子硫醇通过代谢偶联指导林可霉素的生物合成
作者: Zhao QF(赵群飞)1; Wang M(王敏)1; Xu DX(许东啸)1; Zhang QL(张庆林)1; Liu W(刘文)1
通讯作者: 刘文
刊名: Nature
发表日期: 2015
DOI: 10.1038/nature14137
卷: 518, 期:7537, 页:115-119
收录类别: SCI
文章类型: 论文
英文摘要: Low-molecular-mass thiols in organisms are well known for their redox-relevant role in protection against various endogenous and exogenous stresses(1-3). In eukaryotes and Gram-negative bacteria, the primary thiol is glutathione (GSH), a cysteinyl-containing tripeptide. In contrast, mycothiol(MSH), a cysteinyl pseudo-disaccharide, is dominant in Gram-positive actinobacteria, including antibiotic-producing actinomycetes and pathogenic mycobacteria. MSH is equivalent to GSH, either as a cofactor or as a substrate, in numerous biochemical processes(4), most of which have not been characterized, largely due to the dearth of information concerning MSH-dependent proteins. Actinomycetes are able to produce another thiol, ergothioneine (EGT), a histidine betaine derivative that is widely assimilated by plants and animals for variable physiological activities(5). The involvement of EGT in enzymatic reactions, however, lacks any precedent. Here we report that the unprecedented coupling of two bacterial thiols, MSH and EGT, has a constructive role in the biosynthesis of lincomycin A, a sulfur-containing lincosamide (C8 sugar) antibiotic that has been widely used for half a century to treat Gram-positive bacterial infections(6-9). EGT acts as a carrier to template the molecular assembly, and MSH is the sulfur donor for lincomycin maturation after thiol exchange. These thiols function through two unusual S-glycosylations that program lincosamide transfer, activation and modification, providing the first paradigm for EGT-associated biochemical processes and for the poorly understood MSH-dependent biotransformations, a newly described model that is potentially common in the incorporation of sulfur, an element essential for life and ubiquitous in living systems.
语种: 英语
相关网址: 查看原文
WOS记录号: WOS:000349098000043
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内容类型: 期刊论文
URI标识: http://ir.sioc.ac.cn/handle/331003/39485
Appears in Collections:生命有机化学国家重点实验室_期刊论文

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作者单位: 1.中科院上海有机化学研究所, 生命有机化学国家重点实验室
2.湖州生物制造创新中心

Recommended Citation:
Zhao QF,Wang M,Xu DX,et al. Metabolic coupling of two small-molecule thiols programs the biosynthesis of lincomycin A[J]. Nature,2015,518(7537):115-119.
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