DOI: 10.1111/j.1365-2958.2009.06735.x. Coupling of the biosynthesis and export of the DNA gyrase inhibitor simocyclinone in <i>Streptomyces antibioticus</i>

Coupling of the biosynthesis and export of the DNA gyrase inhibitor simocyclinone in Streptomyces antibioticus

10.1111/j.1365-2958.2009.06735.x

Crossref journal-article

Wiley

Molecular Microbiology (311)

Abstract

SummaryBecause most antibiotics are potentially lethal to the producing organism, there must be mechanisms to ensure that the machinery responsible for export of the mature antibiotic is in place at the time of biosynthesis. Simocyclinone D8 is a potent DNA gyrase inhibitor produced by Streptomyces antibioticus Tü 6040. Within the simocyclinone biosynthetic cluster are two divergently transcribed genes, simR and simX, encoding proteins that resemble the TetR/TetA repressor–efflux pump pair that cause widespread resistance to clinically important tetracyclines. Engineered expression of simX from a strong, heterologous promoter conferred high level simocyclinone D8 resistance on Streptomyces lividans, showing that simX encodes a simocyclinone efflux pump. Transcription of simX is controlled by SimR, which directly represses the simX and simR promoters by binding to two operator sites in the simX–simR intergenic region. Simocyclinone D8 abolishes DNA binding by SimR, providing a mechanism that couples the biosynthesis of simocyclinone to its export. In addition, an intermediate in the biosynthetic pathway, simocyclinone C4, which is essentially inactive as a DNA gyrase inhibitor, also induces simX expression in vivo and relieves simX repression by SimR in vitro.

Bibliography

Le, T. B. K., Fiedler, H., Den Hengst, C. D., Ahn, S. K., Maxwell, A., & Buttner, M. J. (2009). Coupling of the biosynthesis and export of the DNA gyrase inhibitor simocyclinone in Streptomyces antibioticus. Molecular Microbiology, 72(6), 1462â1474. Portico.

Authors 6

Tung B. K. Le (first)
Hans‐Peter Fiedler (additional)
Chris D. Den Hengst (additional)
Sang Kyun Ahn (additional)
Anthony Maxwell (additional)
Mark J. Buttner (additional)

References 43 Referenced 40

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Dates

Type	When
Created	16 years, 3 months ago (May 18, 2009, 10:36 a.m.)
Deposited	1 year, 11 months ago (Sept. 28, 2023, 7:18 p.m.)
Indexed	4 months ago (April 30, 2025, 7:27 a.m.)
Issued	16 years, 3 months ago (June 1, 2009)
Published	16 years, 3 months ago (June 1, 2009)
Published Online	16 years, 2 months ago (June 10, 2009)
Published Print	16 years, 3 months ago (June 1, 2009)

Funders 0

None

BibTeX

@article{Le_2009, title={Coupling of the biosynthesis and export of the DNA gyrase inhibitor simocyclinone in Streptomyces antibioticus}, volume={72}, ISSN={1365-2958}, url={http://dx.doi.org/10.1111/j.1365-2958.2009.06735.x}, DOI={10.1111/j.1365-2958.2009.06735.x}, number={6}, journal={Molecular Microbiology}, publisher={Wiley}, author={Le, Tung B. K. and Fiedler, Hans‐Peter and Den Hengst, Chris D. and Ahn, Sang Kyun and Maxwell, Anthony and Buttner, Mark J.}, year={2009}, month=jun, pages={1462–1474} }

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