Carbon catabolite repression (CCR) is a common phenomenon in bacteria that modulates expression of genes involved in uptake of alternative carbon sources. In the filamentous streptomycetes, which produce half of all known antibiotics, the precise mechanism of CCR is yet unknown. We report here that the ROK‐family regulator Rok7B7 pleiotropically controls xylose and glucose uptake, CCR, development, as well as production of the macrolide antibiotics avermectin and oligomycin A in Streptomyces avermitilis. Rok7B7 directly repressed structural genes for avermectin biosynthesis, whereas it activated olmRI, the cluster‐situated activator gene for oligomycin A biosynthesis. Rok7B7 also directly repressed the xylose uptake operon xylFGH, whose expression was induced by xylose and repressed by glucose. Both xylose and glucose served as Rok7B7 ligands. rok7B7 deletion led to enhancement and reduction of avermectin and oligomycin A production, respectively, relieved CCR of xylFGH, and increased co‐uptake efficiency of xylose and glucose. A consensus Rok7B7‐binding site, 5′‐TTKAMKHSTTSAV‐3′, was identified within aveA1p, olmRIp, and xylFp, which allowed prediction of the Rok7B7 regulon and confirmation of 11 additional targets involved in development, secondary metabolism, glucose uptake, and primary metabolic processes. Our findings will facilitate methods for strain improvement, antibiotic overproduction, and co‐uptake of xylose and glucose in Streptomyces species.

中文翻译：

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ROK家族调节剂Rok7B7直接控制阿维链霉菌中碳分解代谢物的阻遏，抗生素的生物合成和形态发育。

碳分解代谢物阻遏（CCR）是细菌中常见的现象，它调节与替代碳源吸收有关的基因的表达。在产生所有已知抗生素一半的丝状链霉菌中，CCR的确切机制尚不清楚。我们在这里报告说，韩国家族调节剂Rok7B7多效控制木糖和葡萄糖摄取，CCR，发育以及阿维链霉菌中大环内酯类抗生素阿维菌素和寡霉素A的产生。Rok7B7直接抑制了阿维菌素生物合成的结构基因，而它激活了寡聚霉素A生物合成的簇状激活基因olmRI。Rok7B7也直接抑制木糖摄取操纵子xylFGH，其表达由木糖诱导并被葡萄糖抑制。木糖和葡萄糖均充当Rok7B7配体。rok7B7缺失分别导致阿维菌素和寡霉素A产生的增加和减少，减轻了xylFGH的CCR ，并提高了木糖和葡萄糖的共摄取效率。在aveA1p，olmRIp和xylFp中鉴定出一个共有的Rok7B7结合位点5'-TTKAMKHSTTSAV-3'，它可以预测Rok7B7调节子并确认与发育，次级代谢，葡萄糖摄取和初级代谢过程有关的11个其他靶标。我们的发现将有助于改进链霉菌属菌株的菌株改良方法，抗生素过量生产以及木糖和葡萄糖的共同摄取。