Regulation of the Synthesis of the Angucyclinone Antibiotic Alpomycin inStreptomyces ambofaciensby the Autoregulator Receptor AlpZ and Its Specific Ligand
10.1128/jb.01989-07
Crossref journal-article
American Society for Microbiology
Journal of Bacteriology (235)
Abstract

ABSTRACTStreptomyces ambofaciensproduces an orange pigment and the antibiotic alpomycin, both of which are products of a type II polyketide synthase gene cluster identified in each of the terminal inverted repeats of the linear chromosome. Five regulatory genes encodingStreptomycesantibiotic regulatory proteins (alpV, previously shown to be an essential activator gene;alpT; andalpU) and TetR family receptors (alpZandalpW) were detected in this cluster. Here, we demonstrate that AlpZ, which shows high similarity to γ-butyrolactone receptors, is at the top of a pathway-specific regulatory hierarchy that prevents synthesis of thealppolyketide products. Deletion of the two copies ofalpZresulted in the precocious production of both alpomycin and the orange pigment, suggesting a repressor role for AlpZ. Consistent with this, expression of the fivealp-located regulatory genes and of two representative biosynthetic structural genes (alpAandalpR) was induced earlier in thealpZdeletion strain. Furthermore, recombinant AlpZ was shown to bind to specific DNA sequences within the promoter regions ofalpZ,alpV, andalpXW, suggesting direct transcriptional control of these genes by AlpZ. Analysis of solvent extracts ofS. ambofacienscultures identified the existence of a factor which induces precocious production of alpomycin and pigment in the wild-type strain and which can disrupt the binding of AlpZ to its DNA targets. This activity is reminiscent of γ-butyrolactone-type molecules. However, the AlpZ-interacting molecule(s) was shown to be resistant to an alkali treatment capable of inactivating γ-butyrolactones, suggesting that the AlpZ ligand(s) does not possess a lactone functional group.

Bibliography

Bunet, R., Mendes, M. V., Rouhier, N., Pang, X., Hotel, L., Leblond, P., & Aigle, B. (2008). Regulation of the Synthesis of the Angucyclinone Antibiotic Alpomycin inStreptomyces ambofaciensby the Autoregulator Receptor AlpZ and Its Specific Ligand. Journal of Bacteriology, 190(9), 3293–3305.

Authors 7
  1. Robert Bunet (first)
  2. Marta V. Mendes (additional)
  3. Nicolas Rouhier (additional)
  4. Xiuhua Pang (additional)
  5. Laurence Hotel (additional)
  6. Pierre Leblond (additional)
  7. Bertrand Aigle (additional)
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Dates
Type When
Created 17 years, 6 months ago (Feb. 22, 2008, 8:54 p.m.)
Deposited 1 year, 6 months ago (Feb. 22, 2024, 12:15 p.m.)
Indexed 2 months, 1 week ago (June 20, 2025, 12:26 p.m.)
Issued 17 years, 3 months ago (May 1, 2008)
Published 17 years, 3 months ago (May 1, 2008)
Published Print 17 years, 3 months ago (May 1, 2008)
Funders 0

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@article{Bunet_2008, title={Regulation of the Synthesis of the Angucyclinone Antibiotic Alpomycin inStreptomyces ambofaciensby the Autoregulator Receptor AlpZ and Its Specific Ligand}, volume={190}, ISSN={1098-5530}, url={http://dx.doi.org/10.1128/jb.01989-07}, DOI={10.1128/jb.01989-07}, number={9}, journal={Journal of Bacteriology}, publisher={American Society for Microbiology}, author={Bunet, Robert and Mendes, Marta V. and Rouhier, Nicolas and Pang, Xiuhua and Hotel, Laurence and Leblond, Pierre and Aigle, Bertrand}, year={2008}, month=may, pages={3293–3305} }