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SACE_3986, a TetR family transcriptional regulator, negatively controls erythromycin biosynthesis in Saccharopolyspora erythraea

  • Panpan Wu
  • Hui Pan
  • Congming Zhang
  • Hang WuEmail author
  • Li Yuan
  • Xunduan Huang
  • Ying Zhou
  • Bang-ce Ye
  • David T. Weaver
  • Lixin Zhang
  • Buchang ZhangEmail author
Genetics and Molecular Biology of Industrial Organisms

Abstract

Erythromycin, a medically important antibiotic, is produced by Saccharopolyspora erythraea. Unusually, the erythromycin biosynthetic gene cluster lacks a regulatory gene, and the regulation of its biosynthesis remains largely unknown. In this study, through gene deletion, complementation and overexpression experiments, we identified a novel TetR family transcriptional regulator SACE_3986 negatively regulating erythromycin biosynthesis in S. erythraea A226. When SACE_3986 was further inactivated in an industrial strain WB, erythromycin A yield of the mutant was increased by 54.2 % in average compared with that of its parent strain, displaying the universality of SACE_3986 as a repressor for erythromycin production in S. erythraea. qRT-PCR analysis indicated that SACE_3986 repressed the transcription of its adjacent gene SACE_3985 (which encodes a short-chain dehydrogenase/reductase), erythromycin biosynthetic gene eryAI and the resistance gene ermE. As determined by EMSA analysis, purified SACE_3986 protein specifically bound to the intergenic region between SACE_3985 and SACE_3986, whereas it did not bind to the promoter regions of eryAI and ermE. Furthermore, overexpression of SACE_3985 in A226 led to enhanced erythromycin A yield by at least 32.6 %. These findings indicate that SACE_3986 is a negative regulator of erythromycin biosynthesis, and the adjacent gene SACE_3985 is one of its target genes. The present study provides a basis to increase erythromycin production by engineering of SACE_3986 and SACE_3985 in S. erythraea.

Keywords

Saccharopolyspora erythraea Erythromycin TetR family transcriptional regulator SACE_3986 SACE_3985 

Notes

Acknowledgments

This work was supported by the National Program on Key Basic Research Project (973 program, 2013CB734000), Open Funding Project of the State Key Laboratory of Bioreactor Engineering (2013), The National Natural Science Foundation of China (31300081, 30870069), The Natural Science Foundation of Anhui Province (1208085MC46), The Initial Foundation of Doctoral Scientific Research in Anhui University (01001904), and The Youth Foundation of Anhui University (02303305).

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Copyright information

© Society for Industrial Microbiology and Biotechnology 2014

Authors and Affiliations

  • Panpan Wu
    • 1
  • Hui Pan
    • 1
  • Congming Zhang
    • 1
  • Hang Wu
    • 1
    Email author
  • Li Yuan
    • 1
  • Xunduan Huang
    • 1
  • Ying Zhou
    • 3
  • Bang-ce Ye
    • 3
  • David T. Weaver
    • 1
  • Lixin Zhang
    • 1
    • 2
  • Buchang Zhang
    • 1
    Email author
  1. 1.Institute of Health Sciences, School of Life SciencesAnhui UniversityHefeiChina
  2. 2.CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of MicrobiologyChinese Academy of SciencesBeijingChina
  3. 3.State Key Laboratory of Bioreactor EngineeringEast China University of Science and TechnologyShanghaiChina

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