An Autoregulated Fine-Tuning Strategy for Titer Improvement of Secondary Metabolites Using Native Promoters in Streptomyces

文献类型： 外文期刊

第一作者： Wang, Junyang

作者： Wang, Junyang;Yang, Keqian;Li, Zilong;Wang, Weishan;Li, Shanshan;Xiang, Wensheng;Wang, Junyang

作者机构：

关键词： Streptomyces;fine-tuning;autoregulation;biosynthetic gene cluster;native promoter;inducible promoter

期刊名称：ACS SYNTHETIC BIOLOGY （ 影响因子：5.11； 五年影响因子：5.239 ）

ISSN： 2161-5063

年卷期： 2018 年 7 卷 2 期

页码：

收录情况： SCI

摘要： Streptomycetes are well-known producers of biologically active secondary metabolites. Various efforts have been made to increase productions of these metabolites, while few approaches could well coordinate the biosynthesis of secondary metabolites and other physiological events of their hosts. Here we develop a universal autoregulated strategy for fine-tuning the expression of secondary metabolites biosynthetic gene clusters (BGCs) in Streptomyces species. First, inducible promoters were used to control the expression of secondary metabolites BGCs. Then, the optimal induction condition was determined by response surface model in both dimensions of time and strength. Finally, native promoters with similar transcription profile to the inducible promoter under the optimal condition were identified based on time-course transcriptome analyses, and used to replace the inducible promoter following an elaborate replacement approach. The expression of actinorhodin (Act) and heterogeneous oxytetracycline (OTC) BGCs were optimized in Streptomyces coelicolor using this strategy. Compared to modulating the expression via constitutive promoters, our strategy could dramatically improve the titers of Act and OTC by 1.3- and 9.1-fold, respectively. The autoregulated fine-tuning strategy developed here opens a novel route for titer improvement of desired secondary metabolites in Streptomyces.

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