Abstract
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
act
II-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
act
II-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
.