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Metabolic coupling of two small-molecule thiols programs the biosynthesis of lincomycin A
Alternative Title两个小分子硫醇通过代谢偶联指导林可霉素的生物合成
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
Source PublicationNature
AbstractLow-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.
Subject Area生命有机化学
Indexed BySCI
WOS IDWOS:000349098000043
Citation statistics
Cited Times:53[WOS]   [WOS Record]     [Related Records in WOS]
Document Type期刊论文
Corresponding AuthorLiu W(刘文)
Affiliation1.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
Recommended Citation
GB/T 7714
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.
APA 赵群飞,王敏,许东啸,张庆林,&刘文.(2015).Metabolic coupling of two small-molecule thiols programs the biosynthesis of lincomycin A.Nature,518(7537),115-119.
MLA 赵群飞,et al."Metabolic coupling of two small-molecule thiols programs the biosynthesis of lincomycin A".Nature 518.7537(2015):115-119.
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