Widespread activation of antibiotic biosynthesis by S-adenosylmethionine in streptomycetes.
The effect of S-adenosylmethionine (SAM) on the production of various antibiotics was investigated to determine whether SAM-dependent methylation is required in biosynthetic pathways of antibiotics. Pristinamycin II(B) and granaticin do not require SAM-dependent methylation in their biosynthesis pathways, and production of these two antibiotics was increased about 2-fold when a low concentration (50 and 10 microM, respectively) of SAM was treated; in contrast, oleandomycin and avermectin B1a require SAM as a methyl donor in their biosynthesis, and production of these two antibiotics was increased 5-fold and 6-fold, depending on the SAM concentration within a certain range. We also found that the transcription of a pathway-specific regulator, gra-ORF9, was activated by exogenous SAM treatment. Production of oleandomycin and avermectin B1a was decreased by using a methyltransferase inhibitor, sinefungin, but the production levels of these antibiotics were restored to the control level by simultaneously adding SAM and sinefungin. Interestingly, we have found a similar stimulatory effect of S-adenosylhomocysteine (SAH), the methylation product of SAM, on antibiotic production in the four strains. Our results clearly demonstrate the widespread activation of antibiotic production using SAM in streptomycetes.
Huh
Jung-Hyun
JH
Department of Biological Science, Institute of Bioscience and Biotechnology, Myongji University, Yongin 449-728, Korea.
Kim
Dong-Jin
DJ
Zhao
Xin-Qing
XQ
Li
Ming
M
Jo
You-Young
YY
Yoon
Tae-Mi
TM
Shin
Su-Kyoung
SK
Yong
Joon-Hyoung
JH
Ryu
Yeon-Woo
YW
Yang
Young-Yell
YY
Suh
Joo-Won
JW
D000900:Anti-Bacterial Agents / Q000096:biosynthesis*; D008745:Methylation / Q000187:drug effects*; D012436:S-Adenosylmethionine / Q000494:pharmacology*; D013306:Streptomycetaceae / Q000187:drug effects* / Q000378:metabolism
D000900:Anti-Bacterial Agents; D012436:S-Adenosylmethionine