A two-component regulatory system involved in clavulanic acid production.
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.
Jnawali
Hum Nath
HN
Institute of Biomolecule Reconstruction (iBR), Department of Pharmaceutical Engineering, SunMoon University.
Oh
Tae-Jin
TJ
Liou
Kwangkyoung
K
Park
Byoung Chul
BC
Sohng
Jae Kyung
JK
D000595:Amino Acid Sequence; D001426:Bacterial Proteins / Q000235:genetics / Q000502:physiology; D019818:Clavulanic Acid / Q000096:biosynthesis*; D004269:DNA, Bacterial / Q000737:chemistry / Q000235:genetics; D017353:Gene Deletion; D018628:Gene Dosage; D015964:Gene Expression Regulation, Bacterial; D023061:Gene Order; D005798:Genes, Bacterial; D005816:Genetic Complementation Test; D008969:Molecular Sequence Data; D005810:Multigene Family; D016415:Sequence Alignment; D017422:Sequence Analysis, DNA; D013302:Streptomyces / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D015534:Trans-Activators / Q000235:genetics / Q000502:physiology*
D001426:Bacterial Proteins; D004269:DNA, Bacterial; D015534:Trans-Activators; D019818:Clavulanic Acid