Accumulation of S-adenosyl-L-methionine enhances production of actinorhodin but inhibits sporulation in Streptomyces lividans TK23.
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.
Kim
Dong-Jin
DJ
Institute of Bioscience and Biotechnology and Department of Biological Science, Myongji University, Yongin 449-728, Korea.
Huh
Jung-Hyun
JH
Yang
Young-Yell
YY
Kang
Choong-Min
CM
Lee
In-Hyung
IH
Hyun
Chang-Gu
CG
Hong
Soon-Kwang
SK
Suh
Joo-Won
JW
D000595:Amino Acid Sequence; D000880:Anthraquinones / Q000378:metabolism*; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism; D003001:Cloning, Molecular; D015964:Gene Expression Regulation, Bacterial; D008716:Methionine Adenosyltransferase / Q000235:genetics* / Q000378:metabolism; D008855:Microscopy, Electron, Scanning; D008969:Molecular Sequence Data; D012436:S-Adenosylmethionine / Q000235:genetics / Q000378:metabolism*; D017422:Sequence Analysis, DNA; D013171:Spores, Bacterial / Q000502:physiology; D013302:Streptomyces / Q000254:growth & development / Q000378:metabolism / Q000502:physiology*; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism; D000095622:Benzoisochromanequinones
D000880:Anthraquinones; D001426:Bacterial Proteins; D008716:Methionine Adenosyltransferase; D012436:S-Adenosylmethionine; D015534:Trans-Activators; C013390:actinorhodin; D000095622:Benzoisochromanequinones