林可霉素的生物合成:两个小分子硫醇的故事
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- 英文论文题名：Lincomycin Biosynthesis:A Tale of Two Small-Molecule Thiols
- 论文作者：赵群飞 ; 王敏 ; 刘文
- 英文论文作者：Qunfei Zhao ; Min Wang ; Wen Liu ; Shanghai Institute of Organic Chemistry ; CAS
- 年：2016
- 作者机构：中国科学院上海有机化学研究所;
- 论文关键词：林可霉素A ; 小分子硫醇 ; 生物合成 ; 糖苷化反应 ; 硫供体
- 会议召开时间：2016-07-01
- 会议录名称：中国化学会第30届学术年会摘要集-第二十八分会：化学生物学
- 语种：中文
- 分类号：TQ465
- 学会代码：ZGHY
- 会议名称：中国化学会第30届学术年会-第二十八分会 ; 化学生物学
- 会议地点：中国辽宁大连
- 主办单位：中国化学会
- 学会名称：中国化学会
- 页数：1
- 文件大小：275k
- 原文格式：D
- 会议级别：全国
摘要
在生物体对抗各种内源性和外源性毒害的过程中,小分子硫醇因其氧化还原作用而扮演的保护性角色已广为人知。近期,在使用长达半个世纪、用于革兰氏阳性细菌感染治疗的林可酰胺类(八碳糖)抗生素林可霉素的生物合成途径中,我们发现两个小分子硫醇MSH和GST通过密切配合扮演了前所未有的建设性角色:GST作为载体介导了活性分子的体内组装,而MSH则在硫醇交换之后成为硫元素的供体。二者以两个罕见的S-糖苷化反应导演了林可酰胺八碳糖的转移、活化和修饰,不但为EGT参与的生化反应过程提供了首个范例,也在迄今为止知之甚少、由MSH介导的生物转化中,建立了广泛存在于生物体系中的必要元素硫原子的渗入机制。
We here report that the unprecedented coupling of two bacterial thiols mycothiol(MSH) and ergothioneine(EGT)plays 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.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 new paradigm that is potentially common in the incorporation of sulfur,an element essential for life and ubiquitous in living systems.
We here report that the unprecedented coupling of two bacterial thiols mycothiol(MSH) and ergothioneine(EGT)plays 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.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 new paradigm that is potentially common in the incorporation of sulfur,an element essential for life and ubiquitous in living systems.
引文
[1]Zhao,Q.;Wang,M.;Xu,D.;Zheng,Q.;Liu,W.Nature 2015,518:115.
[2]Wang,M.;Zhao,Q.;Liu,W.Bioessays 2015,37:1262.
[3]Pang,B.;Wang,M.;Liu,W.Nat.Prod.Rep.2016,33:162.
[2]Wang,M.;Zhao,Q.;Liu,W.Bioessays 2015,37:1262.
[3]Pang,B.;Wang,M.;Liu,W.Nat.Prod.Rep.2016,33:162.