4 years ago

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

An Autoregulated Fine-Tuning Strategy for Titer Improvement of Secondary Metabolites Using Native Promoters in Streptomyces
Keqian Yang, Zilong Li, Shanshan Li, Wensheng Xiang, Junyang Wang, Weishan Wang
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.

Publisher URL: http://dx.doi.org/10.1021/acssynbio.7b00318

DOI: 10.1021/acssynbio.7b00318

You might also like
Discover & Discuss Important Research

Keeping up-to-date with research can feel impossible, with papers being published faster than you'll ever be able to read them. That's where Researcher comes in: we're simplifying discovery and making important discussions happen. With over 19,000 sources, including peer-reviewed journals, preprints, blogs, universities, podcasts and Live events across 10 research areas, you'll never miss what's important to you. It's like social media, but better. Oh, and we should mention - it's free.

  • Download from Google Play
  • Download from App Store
  • Download from AppInChina

Researcher displays publicly available abstracts and doesn’t host any full article content. If the content is open access, we will direct clicks from the abstracts to the publisher website and display the PDF copy on our platform. Clicks to view the full text will be directed to the publisher website, where only users with subscriptions or access through their institution are able to view the full article.