Gamma-butyrolactone-dependent expression of the Streptomyces antibiotic regulatory protein gene srrY plays a central role in the regulatory cascade leading to lankacidin and lankamycin production in Streptomyces rochei.
Our previous studies revealed that the srrX and srrA genes carried on the large linear plasmid pSLA2-L constitute a gamma-butyrolactone-receptor system in Streptomyces rochei. Extensive transcriptional analysis has now showed that the Streptomyces antibiotic regulatory protein gene srrY, which is also carried on pSLA2-L, is a target of the receptor/repressor SrrA and plays a central role in lankacidin and lankamycin production. The srrY gene was expressed in a growth-dependent manner, slightly preceding antibiotic production. The expression of srrY was undetectable in the srrX mutant but was restored in the srrX srrA double mutant. In addition, SrrA was bound specifically to the promoter region of srrY, and this binding was prevented by the addition of the S. rochei gamma-butyrolactone fraction, while the W119A mutant receptor SrrA was kept bound even in the presence of S. rochei gamma-butyrolactone. Furthermore, the introduction of an intact srrY gene under the control of a foreign promoter into the srrX or srrA(W119A) mutant restored antibiotic production. All of these results confirmed the signaling pathway from srrX through srrA to srrY, leading to lankacidin and lankamycin production.
Yamamoto
Shouji
S
Department of Molecular Biotechnology, Graduate School of Advanced Sciences of Matter, Hiroshima University, 1-3-1 Kagamiyama, Higashi-Hiroshima 739-8530, Japan.
He
Yuxi
Y
Arakawa
Kenji
K
Kinashi
Haruyasu
H
D015107:4-Butyrolactone / Q000378:metabolism*; D000900:Anti-Bacterial Agents / Q000096:biosynthesis / Q000378:metabolism; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D001665:Binding Sites; D016172:DNA Fingerprinting; D024202:Electrophoretic Mobility Shift Assay; D004917:Erythromycin / Q000031:analogs & derivatives* / Q000378:metabolism; D015964:Gene Expression Regulation, Bacterial; D005816:Genetic Complementation Test; D018942:Macrolides / Q000378:metabolism*; D016296:Mutagenesis; D009154:Mutation; D010957:Plasmids / Q000235:genetics; D016133:Polymerase Chain Reaction; D011485:Protein Binding; D013302:Streptomyces / Q000235:genetics / Q000254:growth & development / Q000378:metabolism*
D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D018942:Macrolides; C008250:lankacidins; D004917:Erythromycin; C100149:kujimycin B; D015107:4-Butyrolactone