ArticleNature2015
Metabolic coupling of two small-molecule thiols programs the biosynthesis of lincomycin A.
Article in Nature, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers.
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Who cites it
47 citing papers in PubMed, 133 citations in OpenAlex.
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- Molecular basis for the diversification of lincosamide biosynthesis by pyridoxal phosphate-dependent enzymes.Nature chemistry · 2025Article
- A natural killer cell mimic against intracellular pathogen infections.Science advances · 2024Article
- Coupled strategy based on regulator manipulation and medium optimization empowers the biosynthetic overproduction of lincomycin.Synthetic and systems biotechnology · 2024Article
- Three new LmbU targets outside lmb cluster inhibit lincomycin biosynthesis in Streptomyces lincolnensis.Microbial cell factories · 2024Article
- Emerging roles of low-molecular-weight thiols at the host-microbe interface.Current opinion in chemical biology · 2023Review
- Discovery and Characterization of the Metallopterin-Dependent Ergothioneine Synthase fromJACS Au · 2022Article
- Ergothioneine: A Stress Vitamin with Antiaging, Vascular, and Neuroprotective Roles?Antioxidants & redox signaling · 2022Review
- A Fluorescent Probe to Detect Quick Disulfide Reductase Activity in Bacteria.Antioxidants (Basel, Switzerland) · 2022Article
- C-Glycoside metabolism in the gut and in nature: Identification, characterization, structural analyses and distribution of C-C bond-cleaving enzymes.Nature communications · 2021Article
- Thiocysteine lyases as polyketide synthase domains installing hydropersulfide into natural products and a hydropersulfide methyltransferase.Nature communications · 2021Article
- Discovery of Mycothiogranaticins from Streptomyces vietnamensis GIMV4.0001 and the Regulatory Effect of Mycothiol on the Granaticin Biosynthesis.Frontiers in chemistry · 2021Article
- The biology of ergothioneine, an antioxidant nutraceutical.Nutrition research reviews · 2020Review
- Studies of lincosamide formation complete the biosynthetic pathway for lincomycin A.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
- Comparative transcriptomic analysis reveals the significant pleiotropic regulatory effects of LmbU on lincomycin biosynthesis.Microbial cell factories · 2020Article
- Article
- The role of thiols in antioxidant systems.Free radical biology & medicine · 2019Review
- A diversity-oriented rhodamine library for wide-spectrum bactericidal agents with low inducible resistance against resistant pathogens.Nature communications · 2019Article
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Low-molecular-mass thiols in organisms are well known for their redox-relevant role in protection against various endogenous and exogenous stresses. 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, 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. 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. 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.
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