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Applied Microbiology and Biotechnology

, Volume 103, Issue 17, pp 7097–7110 | Cite as

Effect of “ribosome engineering” on the transcription level and production of S. albus indigenous secondary metabolites

  • Maria Lopatniuk
  • Maksym Myronovskyi
  • Alessia Nottebrock
  • Tobias Busche
  • Jörn Kalinowski
  • Bohdan Ostash
  • Viktor Fedorenko
  • Andriy LuzhetskyyEmail author
Applied genetics and molecular biotechnology

Abstract

Significant resources are invested into efforts to improve the production yields of natural products from Actinobacteria, a well-recognized source of leads for several industries, most notably pharmaceutical one. Introduction of changes into genes for ribosomal protein S12 (rpsL) and/or 16S rRNA methylation (rsmG) is one of traditional approaches (referred to as ribosomal engineering) towards actinobacterial strain improvement. Yet, true potential of ribosome engineering remains unknown as it is currently coupled to empirical selection for aminoglycoside-resistance; rpsL mutations without such phenotypic expression could not be isolated. Here, we report a systematic and rational ribosome engineering approach to study the effect of a range of rpsL mutations on the production level of different biosynthetic gene clusters (BGC). The severe effect of diverse rpsL mutations together with deletion of rsmG engineered in Streptomyces albus has been revealed on the transcription level of several indigenous BGCs. The aforementioned mutations strongly impacted the transcription of indigenous BGCs, possibly because they alter the transcription of BGC-situated and global regulatory genes. The rsmG deletion with certain rpsL mutations can have a synergistic effect on the transcription level of indigenous BGCs. Our work thus provides the first streptomycete platform for rational engineering and study of virtually any nonlethal rpsL mutation. The tremendous effect of ribosome engineering on the transcription profile of the strains was reported for the first time. A library of described S. albus rpsL*/ΔrsmG strains represents a useful tool for overproducing known secondary metabolites and activating silent biosynthetic gene clusters in Actinobacteria.

Keywords

Rational ribosome engineering Natural products Transcription profile Streptomyces 

Notes

Funding information

This work was supported by the ERC starting grant EXPLOGEN No. 281623, BMBF grant „MyBio“ 031B0344B to AL and DAAD scholarship Referat: 322 PZK: A/12/84540 to ML.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

This article does not contain studies with human participants or animals performed by any of authors.

Supplementary material

253_2019_10005_MOESM1_ESM.pdf (1.3 mb)
ESM 1 (PDF 1316 kb)

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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  • Maria Lopatniuk
    • 1
  • Maksym Myronovskyi
    • 1
  • Alessia Nottebrock
    • 1
  • Tobias Busche
    • 2
  • Jörn Kalinowski
    • 2
  • Bohdan Ostash
    • 3
  • Viktor Fedorenko
    • 3
  • Andriy Luzhetskyy
    • 1
    • 4
    Email author
  1. 1.Department Pharmacy, Actinobacteria Metabolic Engineering GroupSaarland UniversitySaarbrückenGermany
  2. 2.Centre for Biotechnology (CiBiTec)Bielefeld UniversityBielefeldGermany
  3. 3.Department of Genetics and BiotechnologyIvan Franko National University of LvivLvivUkraine
  4. 4.Helmholtz-Institute for Pharmaceutical Research Saarland (HIPS)SaarbrückenGermany

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