Transcriptional regulation of a leucine-responsive regulatory protein for directly controlling lincomycin biosynthesis in Streptomyces lincolnensis
Transcriptional regulation of a leucine-responsive regulatory protein for directly controlling lincomycin biosynthesis in Streptomyces lincolnensis
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直接控制林肯链霉菌中林可霉素生物合成的亮氨酸响应调节蛋白的转录调控
DOI：
10.1007/s00253-020-10381-w
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发表时间：
2020-01
影响因子：
5
通讯作者：
Buchang Zhang
中科院分区：
文献类型：
--
作者：
Yurong Xu;Yaqian Tang;Nian Wang;Jing Liu;Xinlu Cai;Hongyi Cai;Jie Li;Guoqing Tan;Ruihua Liu;Linquan Bai;Lixin Zhang;Hang Wu;Buchang Zhang
亮氨酸应答调节蛋白(LRPs)是一类参与细菌多种生物学过程的转录因子家族。到目前为止，LRPs调节放线菌中抗生素生物合成的分子机制还很大程度上是未知的。本研究首次在林可链霉菌中鉴定了一个与林可霉素产生相关的LRP(命名为SLCG_LRP)。SLCG_LRP通过直接刺激林可霉素生物合成基因簇中两个结构基因(LMBA和LMBV)、三个抗性基因(LmRA、LmrB和LMRC)和一个调控基因(LmbU)的转录，证明SLCG_LRP是林可霉素生物合成的正调控基因。SLCG_LRP在转录上是自我抑制的，并触发其邻近基因SLCG_3127的表达，该基因编码一个Lyse超家族蛋白。进一步确定了SLCG_3127与SLCG_LRP基因间隔区中SLCG_LRP的结合部位。在林肯链霉菌中，SLCG_3127的失活导致了林可霉素产量的提高，这可能是由于胞内Pro和半胱氨酸的积累所致。精氨酸和苯丙氨酸分别被确定为特异性调节配体，以降低和提高SLCG_LRP与DNA的结合亲和力。我们进一步发现SLCG_LRP可被SLCG_2919直接抑制，SLCG_2919是第一个在LIN簇外发现的林可霉素产生转录因子。因此，我们的研究结果揭示了SLCG_LRP介导的林可霉素生物合成的转录调控。这项研究扩大了对林可霉素生物合成调控的分子机制的理解。
Leucine-responsive regulatory proteins (Lrps) are a family of transcription factors involved in diverse biological processes in bacteria. So far, molecular mechanism of Lrps for regulating antibiotics biosynthesis in actinomycetes remains largely unexplored. This study, for the first time in Streptomyces lincolnensis, identified an Lrp (named as SLCG_Lrp) associated with lincomycin production. SLCG_Lrp was validated to be a positive regulator for lincomycin biosynthesis by directly stimulating transcription of two structural genes (lmbA and lmbV), three resistance genes (lmrA, lmrB and lmrC), and a regulatory gene (lmbU) within the lincomycin biosynthetic gene (lin) cluster. SLCG_Lrp was transcriptionally self-inhibited and triggered the expression of its adjacent gene SLCG_3127 encoding a LysE superfamily protein. Further, the binding site of SLCG_Lrp in the intergenic region of SLCG_3127 and SLCG_Lrp was precisely identified. Inactivation of SLCG_3127 in S. lincolnensis resulted in yield improvement of lincomycin, which was caused by intracellular accumulation of proline and cysteine. Arginine and phenylalanine were identified as specific regulatory ligands, respectively, to reduce and promote DNA-binding affinity of SLCG_Lrp. We further found that SLCG_Lrp was directly repressed by SLCG_2919, the first identified transcription factor outside lin cluster for lincomycin production. Therefore, our findings revealed SLCG_Lrp-mediated transcriptional regulation of lincomycin biosynthesis. This study extends the understanding of molecular mechanisms underlying lincomycin biosynthetic regulation.
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TetR 家族调节因子 SACE_7301 的解剖和工程设计，用于增强红霉素糖多孢菌的产量。
影响因子：
6.4
作者：
Wu H;Chen M;Mao Y;Li W;Liu J;Huang X;Zhou Y;Ye BC;Zhang L;Weaver DT;Zhang B
通讯作者：
Zhang B
DOI：
--
发表时间：
2006-04
期刊：
Journal of biomolecular techniques : JBT
影响因子：
--
作者：
M. Zianni;K. Tessanne;M. Merighi;R. Laguna;F. Tabita
通讯作者：
M. Zianni;K. Tessanne;M. Merighi;R. Laguna;F. Tabita
影响因子：
11
作者：
Ho YC;Hung FR;Weng CH;Li WT;Chuang TH;Liu TL;Lin CY;Lo CJ;Chen CL;Chen JW;Hashimoto M;Hor LI
通讯作者：
Hor LI
影响因子：
2.8
作者：
Kohei Ihara;Kazuki Sato;Hatsuhiro Hori;Y. Makino;S. Shigenobu;T. Ando;E. Isogai;H. Yoneyama
通讯作者：
Kohei Ihara;Kazuki Sato;Hatsuhiro Hori;Y. Makino;S. Shigenobu;T. Ando;E. Isogai;H. Yoneyama
影响因子：
3.2
作者：
Jeong, Ji-A;Hyun, Jaekyung;Oh, Jeong-Il
通讯作者：
Oh, Jeong-Il