Evidence of a role for CutRS and actinorhodin in the secretion stress response in Streptomyces coelicolor M145.
Evidence of a role for CutRS and actinorhodin in the secretion stress response in Streptomyces coelicolor M145.
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DOI：
10.1099/mic.0.001358
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发表时间：
2023-07
期刊：
影响因子：
2.8
通讯作者：
Hutchings, Matthew I.
中科院分区：
文献类型：
--
作者：
McLean, Thomas C.;Beaton, Ainsley D. M.;Martins, Carlo;Saalbach, Gerhard;Chandra, Govind;Wilkinson, Barrie;Hutchings, Matthew I.
关键词：
CutRS是第一个被发现的双组分系统， 链霉菌 种，并在本属中高度保守。早在25年前就有报道说，cutRS的缺失增加了抗生素放线菌紫素的产量， 天蓝色链霉菌然而，尽管有这些早期的工作，CutRS的功能直到现在仍然是个谜。在这里，我们表明，删除cutRS上调放线菌红素生物合成酶的生产高达300倍，解释放线菌红素生产的增加。然而，尽管ChIP-seq在大肠杆菌中鉴定了85个CutR结合位点， S. coelicolor 这些都不在放线菌紫素生物合成基因簇中，这意味着这种影响是间接的。在这项研究中确定的直接调节的CutR目标涉及细胞外蛋白质折叠，包括四个高度保守的HtrA家族折叠酶中的两个：HtrA 3和HtrB，以及一个假定的VKOR酶，预测其在分泌蛋白中催化二硫键形成后回收DsbA。因此，我们试探性地提出了一个作用，CutRS在传感和响应细胞外的蛋白质错误折叠。由于放线菌紫素可以氧化半胱氨酸残基并诱导蛋白质中的二硫键形成，因此其在CycutRS突变体中的过度产生可能是对膜的细胞外表面上的蛋白质错误折叠的响应。
CutRS was the first two-component system to be identified in Streptomyces species and is highly conserved in this genus. It was reported >25 years ago that deletion of cutRS increases the production of the antibiotic actinorhodin in Streptomyces coelicolor . However, despite this early work, the function of CutRS has remained enigmatic until now. Here we show that deletion of cutRS upregulates the production of the actinorhodin biosynthetic enzymes up to 300-fold, explaining the increase in actinorhodin production. However, while ChIP-seq identified 85 CutR binding sites in S. coelicolor none of these are in the actinorhodin biosynthetic gene cluster, meaning the effect is indirect. The directly regulated CutR targets identified in this study are implicated in extracellular protein folding, including two of the four highly conserved HtrA-family foldases: HtrA3 and HtrB, and a putative VKOR enzyme, which is predicted to recycle DsbA following its catalysis of disulphide bond formation in secreted proteins. Thus, we tentatively propose a role for CutRS in sensing and responding to protein misfolding outside the cell. Since actinorhodin can oxidise cysteine residues and induce disulphide bond formation in proteins, its over production in the ∆cutRS mutant may be a response to protein misfolding on the extracellular face of the membrane.
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影响因子：
3.7
作者：
Engler, Carola;Kandzia, Romy;Marillonnet, Sylvestre
通讯作者：
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影响因子：
14.9
作者：
Perez-Riverol Y;Bai J;Bandla C;García-Seisdedos D;Hewapathirana S;Kamatchinathan S;Kundu DJ;Prakash A;Frericks-Zipper A;Eisenacher M;Walzer M;Wang S;Brazma A;Vizcaíno JA
通讯作者：
Vizcaíno JA
影响因子：
3.9
作者：
Feeney, Morgan Anne;Newitt, Jake Terry;Addington, Emily;Algora-Gallardo, Lis;Allan, Craig;Balis, Lucas;Birke, Anna S.;Castano-Espriu, Laia;Charkoudian, Louise K.;Devine, Rebecca;Gayrard, Damien;Hamilton, Jacob;Hennrich, Oliver;Hoskisson, Paul A.;Keith-Baker, Molly;Klein, Joshua G.;Kruasuwan, Worarat;Mark, David R.;Mast, Yvonne;McHugh, Rebecca E.;McLean, Thomas C.;Mohit, Elmira;Munnoch, John T.;Murray, Jordan;Noble, Katie;Otani, Hiroshi;Parra, Jonathan;Pereira, Camila F.;Perry, Louisa;Pintor-Escobar, Linamaria;Pritchard, Leighton;Prudence, Samuel M. M.;Russell, Alicia H.;Schniete, Jana K.;Seipke, Ryan F.;Selem-Mojica, Nelly;Undabarrena, Agustina;Vind, Kristiina;van Wezel, Gilles P.;Wilkinson, Barrie;Worsley, Sarah F.;Duncan, Katherine R.;Fernandez-Martinez, Lorena T.;Hutchings, Matthew I.
通讯作者：
Hutchings, Matthew I.
影响因子：
48
作者：
Gibson, Daniel G.;Young, Lei;Smith, Hamilton O.
通讯作者：
Smith, Hamilton O.
影响因子：
4.8
作者：
Hong, HJ;Hutchings, MI;Buttner, MJ
通讯作者：
Buttner, MJ