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Journal of Bacteriology, January 2003, p. 592-600, Vol. 185, No. 2
0021-9193/03/$08.00+0     DOI: 10.1128/JB.185.2.592-600.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

Accumulation of S-Adenosyl-L-Methionine Enhances Production of Actinorhodin but Inhibits Sporulation in Streptomyces lividans TK23

Dong-Jin Kim,1 Jung-Hyun Huh,1 Young-Yell Yang,1 Choong-Min Kang,1 In-Hyung Lee,2 Chang-Gu Hyun,1 Soon-Kwang Hong,1 and Joo-Won Suh1*

Institute of Bioscience and Biotechnology and Department of Biological Science, Myongji University, Yongin 449-728,1 Food and Life Science Major, School of Techno Science, Kookmin University, Seoul 136-702, Korea2

Received 19 June 2002/ Accepted 2 September 2002

S-Adenosyl-L-methionine synthetase (SAM-s) catalyzes the biosynthesis of SAM from ATP and L-methionine. Despite extensive research with many organisms, its role in Streptomyces sp. remains unclear. In the present study, the putative SAM-s gene was isolated from a spectinomycin producer, Streptomyces spectabilis. The purified protein from the transformed Escherichia coli with the isolated gene synthesized SAM from L-methionine and ATP in vitro, strongly indicating that the isolated gene indeed encoded the SAM-s protein. The overexpression of the SAM-s gene in Streptomyces lividans TK23 inhibited sporulation and aerial mycelium formation but enhanced the production of actinorhodin in both agar plates and liquid media. Surprisingly, the overexpressed SAM was proven by Northern analysis to increase the production of actinorhodin through the induction of actII-ORF4, a transcription activator of actinorhodin biosynthetic gene clusters. In addition, we found that a certain level of intracellular SAM is critical for the induction of antibiotic biosynthetic genes, since the control strain harboring only the plasmid DNA did not show any induction of actII-ORF4 until it reached a certain level of SAM in the cell. From these results, we concluded that the SAM plays important roles as an intracellular factor in both cellular differentiation and antibiotic production in Streptomyces sp.

* Corresponding author. Mailing address: Department of Biological Science, Myongji University, San 38-2, Nam-dong, Yongin 449-728, Korea. Phone: 82-31-330-6190. Fax: 82-31-336-0870. E-mail: jwsuh{at}mju.ac.kr.

Journal of Bacteriology, January 2003, p. 592-600, Vol. 185, No. 2
0021-9193/03/$08.00+0     DOI: 10.1128/JB.185.2.592-600.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.



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