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

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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.

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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.

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Correspondence to Bohdan Ostash.

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

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Yushchuk, O., Ostash, I., Vlasiuk, I. et al. Heterologous AdpA transcription factors enhance landomycin production in Streptomyces cyanogenus S136 under a broad range of growth conditions. Appl Microbiol Biotechnol 102, 8419–8428 (2018).

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