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Developing an endogenous quorum-sensing based CRISPRi circuit for autonomous and tunable dynamic regulation of multiple targets in industrial Streptomyces

biorxiv. 2020; 
Jinzhong Tian,  Gaohua Yang,  Yang Gu,  Xinqiang Sun,  Yinhua Lu,  Weihong Jiang
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摘要

Dynamic regulation has emerged as an effective strategy to improve product titers by balancing metabolic networks, which can be implemented by coupling gene expression to pathway-independent regulatory elements, such as quorum-sensing (QS) systems. However, these QS-based circuits are often created on heterologous systems and must be carefully tuned through tedious testing and optimization process to make them work well, which hampers their application in industrial microbes including streptomycetes. In this study, we design a pathway-independent QS circuit by directly integrating an endogenous QS system with CRISPRi (named EQCi) in the industrial rapamycin-producing strain Streptomyces rapamycinicus. EQCi has... More

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