The leucine-responsive regulatory protein SCAB_Lrp modulates thaxtomin biosynthesis, pathogenicity, and morphological development in Streptomyces scabies.
The leucine-responsive regulatory protein SCAB_Lrp modulates thaxtomin biosynthesis, pathogenicity, and morphological development in Streptomyces scabies.
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DOI：
10.1111/mpp.13285
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发表时间：
2023-02
影响因子：
4.9
通讯作者：
Zhang, Buchang
中科院分区：
文献类型：
--
作者：
Liu, Jing;Wang, Yunxia;He, Haoyang;Dong, Shengnan;Tang, Lijuan;Yang, Endong;Wang, Weiyun;Zhang, Buchang
关键词：
疥疮链霉菌（Streptomyces scabies）是植物致病性最强的链霉菌，是链霉菌大属中的特殊种。疥疮的致病性依赖于次生代谢物萨克托明a的产生，对于萨克托明在疥疮中生物合成的调控机制，除了途径特异性激活剂TxtR和纤维素利用抑制因子CebR之外，目前还知之甚少。亮氨酸反应调节蛋白（Lrp）家族调节非致病性链菌的次生代谢。然而，Lrp与致病链菌之间的调控关系尚不清楚。在这项研究中，我们证明了疥疮S. SCAB_Lrp （SCAB_77931）显著影响了萨氏菌素的生物合成、致病性和形态发育。SCAB_Lrp缺失导致s疥疮的thaxtomin a产量急剧下降和低毒力表型。对SCAB_Lrp调控机制的深入剖析表明，它通过直接结合簇上调控基因txtR的启动子，正向调控thaxtomin生物合成基因簇的转录。SCAB_Lrp还通过直接激活amfC、whb和ssgB的转录来控制疥疮的形态发育。SCAB_Lrp通过结合特定序列（5′‐GGACAGTCGCCGTGCTACG‐3′）直接控制自身基因的转录。此外，苯丙氨酸和蛋氨酸通过增强SCAB_Lrp与DNA的结合亲和力和复合物状态而被表征为SCAB_Lrp的效应物。我们的研究结果表征了一种多功能调节蛋白——SCAB_Lrp，它控制着s.s疥疮的次生代谢、致病性和产孢，并为致病链霉菌调节萨氏菌素植物毒素的复杂调节网络提供了新的见解。来自致病性疥疮链霉菌的SCAB_Lrp通过直接控制txtR、amfC、whb和ssgB的转录，积极影响萨氏菌素的生物合成、致病性和形态发育。
Streptomyces scabies is the best‐characterized plant‐pathogenic streptomycete, which is a special species among the large genus Streptomyces. The pathogenicity of S. scabies relies on the production of the secondary metabolite thaxtomin A. Little is known about the molecular mechanisms underlying the regulation of thaxtomin biosynthesis in S. scabies beyond the pathway‐specific activator TxtR and the cellulose utilization repressor CebR. The leucine‐responsive regulatory protein (Lrp) family modulates secondary metabolism in nonpathogenic streptomycetes. However, the regulatory relationship between the Lrp and pathogenic streptomycetes remains unknown. In this study, we demonstrated that SCAB_Lrp (SCAB_77931) from S. scabies significantly affects thaxtomin biosynthesis, pathogenicity, and morphological development. SCAB_Lrp deletion resulted in a dramatic decline in thaxtomin A production and a low‐virulence phenotype of S. scabies. An in‐depth dissection of the regulatory mechanism of SCAB_Lrp revealed that it positively regulates the transcription of the thaxtomin biosynthetic gene cluster by directly binding to the promoter of the cluster‐situated regulator gene txtR. SCAB_Lrp also controls the morphological development of S. scabies by directly activating the transcription of amfC, whiB, and ssgB. SCAB_Lrp directly controls the transcription of its own gene by binding a specific sequence (5′‐GGACAGTCGCCGTGCTACG‐3′). Moreover, phenylalanine and methionine have been characterized as SCAB_Lrp effectors by strengthening the binding affinity and complex status between SCAB_Lrp and DNA. Our findings characterize a multifunctional regulatory protein, SCAB_Lrp, that controls secondary metabolism, pathogenicity, and sporulation in S. scabies and provide new insights into the complex regulatory network that modulates thaxtomin phytotoxins in pathogenic Streptomyces. SCAB_Lrp from pathogenic Streptomyces scabies positively affects thaxtomin biosynthesis, pathogenicity, and morphological development by directly controlling the transcription of txtR, amfC, whiB, and ssgB.
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