ArticleMicrobial cell factories2020
Comparative transcriptomic analysis reveals the significant pleiotropic regulatory effects of LmbU on lincomycin biosynthesis.
Article in Microbial cell factories, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.
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5 citing papers in PubMed, 19 citations in OpenAlex.
- Transcriptional regulators of secondary metabolite biosynthesis in Streptomyces.World journal of microbiology & biotechnology · 2024Review
- Three new LmbU targets outside lmb cluster inhibit lincomycin biosynthesis in Streptomyces lincolnensis.Microbial cell factories · 2024Article
- PAS domain containing regulator SLCG_7083 involved in morphological development and glucose utilization in Streptomyces lincolnensis.Microbial cell factories · 2023Article
- Roles of LuxR-family regulators in the biosynthesis of secondary metabolites in Actinobacteria.World journal of microbiology & biotechnology · 2022Review
- Modulation of Multiple Gene Clusters' Expression by the PAS-LuxR Transcriptional Regulator PteF.Antibiotics (Basel, Switzerland) · 2022Article
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Authors and funding
5 authors at 2 institutions in 1 country.
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Abstract
backgroundLincomycin, produced by Streptomyces lincolnensis, is a lincosamide antibiotic and widely used for the treatment of the infective diseases caused by Gram-positive bacteria. The mechanisms of lincomycin biosynthesis have been deeply explored in recent years. However, the regulatory effects of LmbU that is a transcriptional regulator in lincomycin biosynthetic (lmb) gene cluster have not been fully addressed.
resultsLmbU was used to search for homologous LmbU (LmbU-like) proteins in the genomes of actinobacteria, and the results showed that LmbU-like proteins are highly distributed regulators in the biosynthetic gene clusters (BGCs) of secondary metabolites or/and out of the BGCs in actinomycetes. The overexpression, inactivation and complementation of the lmbU gene indicated that LmbU positively controls lincomycin biosynthesis in S. lincolnensis. Comparative transcriptomic analysis further revealed that LmbU activates the 28 lmb genes at whole lmb cluster manner. Furthermore, LmbU represses the transcription of the non-lmb gene hpdA in the biosynthesis of L-tyrosine, the precursor of lincomycin. LmbU up-regulates nineteen non-lmb genes, which would be involved in multi-drug flux to self-resistance, nitrate and sugar transmembrane transport and utilization, and redox metabolisms.
conclusionsLmbU is a significant pleiotropic transcriptional regulator in lincomycin biosynthesis by entirely activating the lmb cluster and regulating the non-lmb genes in Streptomyces lincolnensis. Our results first revealed the pleiotropic regulatory function of LmbU, and shed new light on the transcriptional effects of LmbU-like family proteins on antibiotic biosynthesis in actinomycetes.
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