title: Widespread activation of antibiotic biosynthesis by S-adenosylmethionine in streptomycetes.
abstract: 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.
authors.affiliation: Department of Biological Science, Institute of Bioscience and Biotechnology, Myongji University, Yongin 449-728, Korea.
authors.forename: Jung-Hyun
authors.initials: JH
authors.lastname: Huh
authors.forename: Dong-Jin
authors.initials: DJ
authors.lastname: Kim
authors.forename: Xin-Qing
authors.initials: XQ
authors.lastname: Zhao
authors.forename: Ming
authors.initials: M
authors.lastname: Li
authors.forename: You-Young
authors.initials: YY
authors.lastname: Jo
authors.forename: Tae-Mi
authors.initials: TM
authors.lastname: Yoon
authors.forename: Su-Kyoung
authors.initials: SK
authors.lastname: Shin
authors.forename: Joon-Hyoung
authors.initials: JH
authors.lastname: Yong
authors.forename: Yeon-Woo
authors.initials: YW
authors.lastname: Ryu
authors.forename: Young-Yell
authors.initials: YY
authors.lastname: Yang
authors.forename: Joo-Won
authors.initials: JW
authors.lastname: Suh
mesh_terms: D000900:Anti-Bacterial Agents / Q000096:biosynthesis*; D008745:Methylation / Q000187:drug effects*; D012436:S-Adenosylmethionine / Q000494:pharmacology*; D013306:Streptomycetaceae / Q000187:drug effects* / Q000378:metabolism
chemical_list: D000900:Anti-Bacterial Agents; D012436:S-Adenosylmethionine