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Journal of Bacteriology, February 2008, p. 1308-1316, Vol. 190, No. 4
0021-9193/08/$08.00+0     doi:10.1128/JB.01383-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

{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{triangledown} ,{dagger}

Shouji Yamamoto, Yuxi He, Kenji Arakawa, and Haruyasu Kinashi*

Department of Molecular Biotechnology, Graduate School of Advanced Sciences of Matter, Hiroshima University, Higashi-Hiroshima, Japan

Received 24 August 2007/ Accepted 5 December 2007

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.

* Corresponding author. Mailing address: Department of Molecular Biotechnology, Graduate School of Advanced Sciences of Matter, Hiroshima University, 1-3-1 Kagamiyama, Higashi-Hiroshima 739-8530, Japan. Phone and fax: 81-82-424-7869. E-mail: kinashi{at}hiroshima-u.ac.jp

{triangledown} Published ahead of print on 14 December 2007.

{dagger} Supplemental material for this article may be found at http://jb.asm.org/.

Journal of Bacteriology, February 2008, p. 1308-1316, Vol. 190, No. 4
0021-9193/08/$08.00+0     doi:10.1128/JB.01383-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.





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