Accumulation ofS-Adenosyl-l-Methionine Enhances Production of Actinorhodin but Inhibits Sporulation inStreptomyces lividansTK23

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 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.

Carbon source regulation of antibiotic production

“…caesius. [199][200][201][202] Although the overall mechanism underlying this activity is not completely understood, the obvious methylation of intermediates leading to the biosynthesis of antibiotics involving SAM provides a strong explanation for the high yield of these compounds. 203 There have been notorious advances in the elucidation of the regulatory mechanisms of antibiotic formation at the biochemical and molecular levels.…”

The aptamer core of SAM-IV riboswitches mimics the ligand-binding site of SAM-I riboswitches

“…riboswitches might be misannotated. Gene regulation of sulfur metabolism is of particular interest in Streptomyces, as SAM levels affect antibiotic production and sporulation in these species (Kim et al 2003;Okamoto et al 2003).…”

Phosphoprotein affinity purification identifies proteins involved in S-adenosyl-L-methionine-induced enhancement of antibiotic production in Streptomyces coelicolor

“…Secondary metabolite production in Streptomyces is usually strain specific; thus, it is difficult to develop a universal method to promote the production of secondary metabolites in most Streptomyces strains. 1,2 We observed that increased concentration of S-adenosylmethionine (SAM) by overexpression of SAM synthetase gene stimulated actinorhodin production in Streptomyces lividans, 3,4 and exogenous SAM treatment in culture media enhanced streptomycin production in S. griseus, 5 as well as other secondary metabolite production in many Streptomyces strains. 6 On the basis of these results, we sought to identify SAM-response proteins, which might be targets, to improve secondary metabolite production in many Streptomyces spp.…”