| 刘晶,李通,刘增智,等.通过阻断GntR家族调控基因ygrA挖掘海洋链霉菌Streptomyces sp. OUC6819中抗MDR菌活性次级代谢产物[J].中国海洋药物,2017,36(5):16-22. |
| 通过阻断GntR家族调控基因ygrA挖掘海洋链霉菌Streptomyces sp. OUC6819中抗MDR菌活性次级代谢产物 |
| Mining anti-MDRB compounds from mangrove-derived Streptomyces sp. OUC6819 by inactivation of GntR family regulatory gene ygrA |
| 投稿时间：2017-03-08 修订日期：2017-04-18 |
| DOI： |
| 中文关键词: Streptomyces sp. OUC6819 PCR-targeting GntR家族调控基因 多重耐药菌 |
| English Keywords:Streptomyces sp. OUC6819 PCR-targeting GntR family regulator multi-drug resistant bacteria (MDRB) |
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| 中文摘要: |
| 激活南海红树林来源链霉菌Streptomyces sp.OUC6819菌株中不表达或表达量低的隐性生物合成基因簇，挖掘具有优良多重耐药菌（MDR）抗菌活性的次级代谢产物。方法 通过生物信息学分析推测Streptomyces sp.OUC6819基因组中可能的GntR家族调控子，采用PCR-targeting策略敲除其中的ygrA基因，HPLC分析突变株和野生株的发酵产物的差异，并比较粗提物对5株MDR菌抑制活性。结果 HPLC分析结果表明与野生株相比，突变株中化合物1和化合物2产量分别产量提高了9倍和7倍；突变株发酵液粗提物对其中3株MDR菌抑制活性较野生株明显提高。结论 通过阻断GntR家族调控子ygrA激活了Streptomyces sp.OUC6819菌株中具有抗MDR菌活性次级代谢产物合成基因簇的表达，为从中发掘新的抗MDR菌抗生素奠定了必要基础；同时，将为其他海洋链霉菌中隐性基因簇的激活提供重要参考。 |
| English Summary: |
| To activate cryptic biosynthetic gene clusters in mangrove-derived Streptomyces sp. OUC6819, and thus to discover anti-MDR (multi-drug resistant) bacteria secondary metabolites. Methods Genome scanning of Streptomyces sp. OUC6819 disclosed many GntR family regulators, among which ygrA gene was knocked out by using PCR-targeting strategy. The resulting fermentation broths were analyzed by HPLC. In addition, the crude extracts were subjected to bioassay against five MDRB strains. Results HPLC analysis suggested that the yields of compound 1 and 2 were increased by about 9- and 7-fold, respectively, in the ΔygrA strain compared to the wild-type strain. The crude extract from the mutant strain exhibited much stronger inhibition activities against three MDRB strains. Conclusion By inactivating the GntR family regulatory gene ygrA, the biosynthetic gene cluster(s) encoding anti-MDRB compounds was (were) activated, thereby laying the foundation for discovery of new anti-MDRB antibiotics. Moreover, our study provides important reference for activation of cryptic gene clusters in other marine-derived Streptomyces stain. |
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