Precise control of microbial gene expression is crucial for synthetic biotechnological applications. This is particularly true for the bacterial genus Streptomyces, major producers of diverse natural products including many antibiotics. Although a plethora of genetic tools have been developed for Streptomyces, there is still an urgent need for effective gene induction systems. We herein created two novel cellobiose-inducible regulatory systems referred to as Cel-RS1 and Cel-RS2. The regulatory systems are based upon the well-characterized repressor/operator pair CebR/cebO from Streptomyces scabies and the well-defined constitutive kasO* promoter. Both Cel-RS1 and Cel-RS2 exhibit a high level of induced reporter activity and virtually no leaky expression in three model Streptomyces species, which are commonly used as surrogate hosts for expression of natural product biosynthetic gene clusters. Cel-RS2 has been proven successful for programmable control of gene expression and controllable production of specialized metabolites in multiple Streptomyces species. The strategy can be used to expand the toolkit of inducible regulatory systems that will be broadly applicable to various Streptomyces.

中文翻译：

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合成纤维二糖诱导调节系统允许对链霉菌中的基因表达进行严格和动态控制

微生物基因表达的精确控制对于合成生物技术应用至关重要。对于细菌属链霉菌来说尤其如此，链霉菌是多种天然产物的主要生产者，包括许多抗生素。尽管已经为链霉菌开发了大量的遗传工具，但仍然迫切需要有效的基因诱导系统。我们在此创建了两个新的纤维二糖诱导型调节系统，称为Cel-RS1和Cel-RS2。调节系统基于来自Streptomyces scabies 的充分表征的阻遏物/操纵子对 CebR/ cebO和明确定义的组成型 kasO*启动子。两个都Cel-RS1和Cel-RS2在三种模型链霉菌中表现出高水平的诱导报告活性，几乎没有泄漏表达，这些链霉菌通常用作天然产物生物合成基因簇表达的替代宿主。Cel-RS2已被证明在多种链霉菌中基因表达的可编程控制和特殊代谢物的可控生产方面是成功的。该策略可用于扩展可广泛适用于各种链霉菌的诱导型调控系统工具包。