ArticlePloS one2015
Lincosamide synthetase--a unique condensation system combining elements of nonribosomal peptide synthetase and mycothiol metabolism.
Article in PloS one, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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15 citing papers in PubMed, 30 citations in OpenAlex.
- Translating biosynthetic gene cluster architecture into biosensor design for microbial natural product discovery.Essays in biochemistry · 2026Review
- Kineochelins-A New Group of Siderophores From an Antarctic Bacterium.Microbial biotechnology · 2026Article
- Recent advances in lincosamide biosynthetic studies.The Journal of antibiotics · 2026Review
- Molecular basis for the diversification of lincosamide biosynthesis by pyridoxal phosphate-dependent enzymes.Nature chemistry · 2025Article
- Chemometrics and genome mining reveal an unprecedented family of sugar acid-containing fungal nonribosomal cyclodepsipeptides.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Article
- Comparative transcriptomic analysis reveals the significant pleiotropic regulatory effects of LmbU on lincomycin biosynthesis.Microbial cell factories · 2020Article
- Interbacterial mechanisms of colonization resistance and the strategies pathogens use to overcome them.Mucosal immunology · 2019Review
- Enhanced lincomycin production by co-overexpression of metK1 and metK2 in Streptomyces lincolnensis.Journal of industrial microbiology & biotechnology · 2018Article
- Caboxamycin biosynthesis pathway and identification of novel benzoxazoles produced by cross-talk in Streptomyces sp. NTK 937.Microbial biotechnology · 2017Article
- Elucidation of salicylate attachment in celesticetin biosynthesis opens the door to create a library of more efficient hybrid lincosamide antibiotics.Chemical science · 2017Article
- Evolution-guided adaptation of an adenylation domain substrate specificity to an unusual amino acid.PloS one · 2017Article
- Characterization of Enzymes Catalyzing Transformations of Cysteine S-Conjugated Intermediates in the Lincosamide Biosynthetic Pathway.Chembiochem : a European journal of chemical biology · 2016Article
- Deacetylation of mycothiol-derived 'waste product' triggers the last biosynthetic steps of lincosamide antibiotics.Chemical science · 2016Article
- New Concept of the Biosynthesis of 4-Alkyl-L-Proline Precursors of Lincomycin, Hormaomycin, and Pyrrolobenzodiazepines: Could a γ-Glutamyltransferase Cleave the C-C Bond?Frontiers in microbiology · 2016Article
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12 authors at 3 institutions in 2 countries.
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No grant is acknowledged in the PubMed record.
Abstract
In the biosynthesis of lincosamide antibiotics lincomycin and celesticetin, the amino acid and amino sugar units are linked by an amide bond. The respective condensing enzyme lincosamide synthetase (LS) is expected to be an unusual system combining nonribosomal peptide synthetase (NRPS) components with so far unknown amino sugar related activities. The biosynthetic gene cluster of celesticetin was sequenced and compared to the lincomycin one revealing putative LS coding ORFs shared in both clusters. Based on a bioassay and production profiles of S. lincolnensis strains with individually deleted putative LS coding genes, the proteins LmbC, D, E, F and V were assigned to LS function. Moreover, the newly recognized N-terminal domain of LmbN (LmbN-CP) was also assigned to LS as a NRPS carrier protein (CP). Surprisingly, the homologous CP coding sequence in celesticetin cluster is part of ccbZ gene adjacent to ccbN, the counterpart of lmbN, suggesting the gene rearrangement, evident also from still active internal translation start in lmbN, and indicating the direction of lincosamide biosynthesis evolution. The in vitro test with LmbN-CP, LmbC and the newly identified S. lincolnensis phosphopantetheinyl transferase Slp, confirmed the cooperation of the previously characterized NRPS A-domain LmbC with a holo-LmbN-CP in activation of a 4-propyl-L-proline precursor of lincomycin. This result completed the functional characterization of LS subunits resembling NRPS initiation module. Two of the four remaining putative LS subunits, LmbE/CcbE and LmbV/CcbV, exhibit low but significant homology to enzymes from the metabolism of mycothiol, the NRPS-independent system processing the amino sugar and amino acid units. The functions of particular LS subunits as well as cooperation of both NRPS-based and NRPS-independent LS blocks are discussed. The described condensing enzyme represents a unique hybrid system with overall composition quite dissimilar to any other known enzyme system.
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