Applied Microbiology and Biotechnology

, Volume 102, Issue 19, pp 8419–8428 | Cite as

Heterologous AdpA transcription factors enhance landomycin production in Streptomyces cyanogenus S136 under a broad range of growth conditions

  • Oleksandr Yushchuk
  • Iryna Ostash
  • Iryna Vlasiuk
  • Tetiana Gren
  • Andriy Luzhetskyy
  • Joern Kalinowski
  • Victor Fedorenko
  • Bohdan OstashEmail author
Applied genetics and molecular biotechnology


Streptomyces cyanogenus S136 is the only known producer of landomycin A (LaA), one of the largest glycosylated angucycline antibiotics possessing strong antiproliferative properties. There is rising interest in elucidation of mechanisms of action of landomycins, which, in turn, requires access to large quantities of the pure compounds. Overproduction of LaA has been achieved in the past through manipulation of cluster-situated regulatory genes. However, other components of the LaA biosynthetic regulatory network remain unknown. To fill this gap, we elucidated the contribution of AdpA family pleiotropic regulators in landomycin production via expression of adpA genes of different origins in S. cyanogenus S136. Overexpression of the native S. cyanogenus S136 adpA ortholog had no effect on landomycin titers. In the same time, expression of several heterologous adpA genes led to significantly increased landomycin production under different cultivation conditions. Hence, heterologous adpA genes are a useful tool to enhance or activate landomycin production by S. cyanogenus. Our ongoing research effort is focused on identification of mutations that render S. cyanogenus AdpA nonfunctional.


Streptomyces Landomycin A Regulation AdpA family regulators 



We thank Simon Shaw (Technical University of Denmark, Copenhagen) for careful proofreading of the manuscript.


This work was supported by grants Bg-46F (to V. F.) and M/26-2018 and Bg-41Nr (to B.O.) from the Ministry of Education and Science of Ukraine.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical statement

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

Supplementary material

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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Department of Genetics and BiotechnologyIvan Franko National University of LvivLvivUkraine
  2. 2.Technology Platform Genomics, CeBiTecBielefeld UniversityBielefeldGermany
  3. 3.Department of Pharmaceutical Biotechnology, Helmholtz Institute for Pharmaceutical Research Saarland, Actinobacteria Metabolic Engineering GroupSaarland UniversitySaarbruckenGermany

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