
doi: 10.1038/ja.2008.92
pmid: 19168979
A pair of genes encoding the bacterial two-component regulatory system, orf22 and orf23, was found next to the clavulanic acid gene cluster of Streptomyces clavuligerus NRRL3585. Orf23 was deleted for the construction of S. clavuligerus/Deltaorf23. Although growth and morphological analyses showed no differences between S. clavuligerus/Deltaorf23 and wild-type, the production of clavulanic acid in S. clavuligerus/Deltaorf23 was found to be decreased. In addition, the co-overexpression of orf22/orf23 in wild-type resulted in an enhanced 1.49-fold production of clavulanic acid, and the complementation of orf22/orf23 in S. clavuligerus/Deltaorf23 restored clavulanic acid production about 80% as normal levels. These results demonstrate that the orf22/orf23 two-component regulatory system participates as a positive regulator of the biosynthesis of clavulanic acid and increased levels of orf22/orf23 can contribute to enhanced production of clavulanic acid in S. clavuligerus.
DNA, Bacterial, Genetic Complementation Test, Molecular Sequence Data, Gene Dosage, Gene Expression Regulation, Bacterial, Sequence Analysis, DNA, Streptomyces, Bacterial Proteins, Genes, Bacterial, Multigene Family, Gene Order, Trans-Activators, Amino Acid Sequence, Sequence Alignment, Clavulanic Acid, Gene Deletion
DNA, Bacterial, Genetic Complementation Test, Molecular Sequence Data, Gene Dosage, Gene Expression Regulation, Bacterial, Sequence Analysis, DNA, Streptomyces, Bacterial Proteins, Genes, Bacterial, Multigene Family, Gene Order, Trans-Activators, Amino Acid Sequence, Sequence Alignment, Clavulanic Acid, Gene Deletion
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