BACKGROUND Lincomycin, 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. RESULTS LmbU 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. CONCLUSIONS LmbU 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.

中文翻译：

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比较转录组分析显示LmbU对林可霉素的生物合成具有显着的多效性调节作用。

背景技术林肯链霉菌（Streptomyces lincolnensis）生产的林可霉素是一种林可酰胺抗生素，被广泛用于治疗由革兰氏阳性细菌引起的感染性疾病。近年来，林可霉素的生物合成机制已得到深入研究。但是，在林可霉素生物合成（lmb）基因簇中作为转录调节子的LmbU的调节作用尚未完全解决。结果LmbU被用来在放线菌的基因组中搜索同源的LmbU（LmbU样）蛋白，结果表明LmbU样蛋白在次级代谢产物的生物合成基因簇（BGC）中是高度分布的调节子，或/和放线菌中的BGC。lmbU基因的过度表达，失活和互补表明LmbU阳性控制了S中林可霉素的生物合成。林肯。比较转录组学分析进一步表明，LmbU以整个lmb簇的方式激活了28个lmb基因。此外，LmbU在林可霉素的前体L-酪氨酸的生物合成中抑制了非lmb基因hpdA的转录。LmbU上调19个非lmb基因，这些基因将参与多种药物对自身抗性，硝酸盐和糖跨膜转运和利用以及氧化还原代谢的影响。结论LmbU是林可霉素生物合成中的重要多效转录调节因子，它可以完全激活林肯链霉菌中的lmb簇并调节非lmb基因。我们的研究结果首先揭示了LmbU的多效调节功能，并为LmbU样家族蛋白对放线菌中抗生素生物合成的转录作用提供了新的启示。