A possible mechanism for lincomycin induction of secondary metabolism in Streptomyces coelicolor A3(2)
A possible mechanism for lincomycin induction of secondary metabolism in Streptomyces coelicolor A3(2)
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DOI：
10.1007/s10482-018-1021-0
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发表时间：
2018-01
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影响因子：
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通讯作者：
Misaki Ishizuka;Y. Imai;Keiichiro Mukai;Kazuma Shimono;Ryoko Hamauzu;K. Ochi;T. Hosaka
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文献类型：
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作者：
Misaki Ishizuka;Y. Imai;Keiichiro Mukai;Kazuma Shimono;Ryoko Hamauzu;K. Ochi;T. Hosaka
林可霉素在细菌核糖体50S亚基的23S核糖体RNA(RRNA)的肽基转移酶环区内形成交联键，从而抑制蛋白质的合成。我们以前曾报道，林可霉素浓度低于最低抑制浓度时，可以增强放线菌菌株次生代谢物的产生，这表明利用林可霉素的剂量依赖反应来激活这些菌株可以有效地诱导隐蔽次生代谢物的产生。在这里，我们旨在阐明林可霉素诱导放线菌次生代谢的基本机制。本研究探讨了林可霉素对模型天蓝色链霉菌A3(2)基因表达的剂量依赖性反应及其与次生代谢的可能关系。RNA测序分析表明，林可霉素引起了基因表达谱的巨大变化。此外，逆转录聚合酶链式反应和/或比较蛋白质组分析显示INS。CoelicolorA3(2)，林可霉素，在显著增加蓝色素抗生素放线菌素产量的浓度下，迅速增强编码林可霉素外流ABC转运体、23S rRNA甲基转移酶和核糖体分裂因子的基因的表达，以增强内在的林可霉素抗性机制，并用林可霉素重建可能停滞不前的70年代核糖体；相反，管家基因，如编码FoF1ATP合成酶、RNA聚合酶、核糖体蛋白以及转录和翻译因子的mRNA水平暂时但显著降低，细胞内NTP增加。林可霉素诱导INS次生代谢的可能机制。在此基础上，对天南星A3(2)进行了讨论。
Lincomycin forms cross-links within the peptidyl transferase loop region of the 23S ribosomal RNA (rRNA) of the 50S subunit of the bacterial ribosome, which is the site of peptide bond formation, thereby inhibiting protein synthesis. We have previously reported that lincomycin at concentrations below the minimum inhibitory concentration potentiates the production of secondary metabolites in actinomycete strains, suggesting that activation of these strains by utilizing the dose-dependent response of lincomycin could be used to effectively induce the production of cryptic secondary metabolites. Here, we aimed to elucidate the fundamental mechanisms underlying lincomycin induction of secondary metabolism in actinomycetes. In the present study, the dose-dependent response of lincomycin on gene expression of the model actinomyceteStreptomyces coelicolorA3(2) and possible relationships to secondary metabolism were investigated. RNA sequencing analysis indicated that lincomycin produced enormous changes in gene expression profiles. Moreover, reverse transcription PCR and/or comparative proteome analysis revealed that inS. coelicolorA3(2), lincomycin, which was used at concentrations for markedly increased blue-pigmented antibiotic actinorhodin production, rapidly enhanced expression of the gene encoding the lincomycin-efflux ABC transporter, the 23S rRNA methyltransferase, and the ribosome-splitting factor to boost the intrinsic lincomycin resistance mechanisms and to reconstruct the probably stalled 70S ribosomes with lincomycin; and in contrast temporarily but dramatically reduced mRNA levels of housekeeping genes, such as those encoding FoF1ATP synthase, RNA polymerase, ribosomal proteins, and transcription and translation factors, with an increase in intracellular NTPs. A possible mechanism for lincomycin induction of secondary metabolism inS. coelicolorA3(2) is discussed on the basis of these results.