Applied Microbiology and Biotechnology

, Volume 102, Issue 9, pp 4101–4115 | Cite as

Global regulator BldA regulates morphological differentiation and lincomycin production in Streptomyces lincolnensis

  • Bingbing Hou
  • Liyuan Tao
  • Xiaoyu Zhu
  • Wei Wu
  • Meijin Guo
  • Jiang Ye
  • Haizhen Wu
  • Huizhan Zhang
Applied genetics and molecular biotechnology


Global regulator BldA, the only tRNA for a rare leucine codon UUA, is best known for its ability to affect morphological differentiation and secondary metabolism in the genus Streptomyces. In this study, we confirmed the regulatory function of the bldA gene (Genbank accession no. EU124663.1) in Streptomyces lincolnensis. Disruption of bldA hinders the sporulation and lincomycin production, that can recur when complemented with a functional bldA gene. Western blotting assays demonstrate that translation of the lmbB2 gene which encodes a L-tyrosine hydroxylase is absolutely dependent on BldA; however, mistranslation of the lmbU gene which encodes a cluster-situated regulator (CSR) is observed in a bldA mutant. Intriguingly, when the preferential cognate codon CTG was used, the expression level of LmbU was not the highest compared to the usage of rare codon TTA or CTA, indicating the rare codon in this position is significant for the regulation of lmbU expression. Moreover, replacement of TTA codons in both genes with another leucin codon in the bldA mutant did not restore lincomycin production. Thus, we believe that the bldA gene regulates lincomycin production via controlling the translation of not only lmbB2 and lmbU, but also the other TTA-containing genes. In conclusion, the present study demonstrated the importance of the bldA gene in morphological differentiation and lincomycin production in S. lincolnensis.


S. lincolnensis bldA Leucine codon Morphological differentiation Lincomycin production Regulatory pathway 


Funding information

This work was supported by the National Natural Science Foundation of China (NSFS) (3120026).

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

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

Supplementary material

253_2018_8900_MOESM1_ESM.pdf (874 kb)
ESM 1 (PDF 873 kb)


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Copyright information

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

Authors and Affiliations

  • Bingbing Hou
    • 1
  • Liyuan Tao
    • 1
  • Xiaoyu Zhu
    • 1
  • Wei Wu
    • 1
  • Meijin Guo
    • 1
  • Jiang Ye
    • 2
  • Haizhen Wu
    • 1
    • 2
  • Huizhan Zhang
    • 1
    • 2
  1. 1.State Key Laboratory of Bioreactor EngineeringEast China University of Science and TechnologyShanghaiChina
  2. 2.Department of Applied BiologyEast China University of Science and TechnologyShanghaiChina

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