Widespread activation of antibiotic blosynthesis by S-adenosylmethionine in streptomycetes

Widespread activation of antibiotic blosynthesis by S-adenosylmethionine in streptomycetes
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DOI:
10.1016/j.femsle.2004.08.009
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发表时间:
2004-09-15
影响因子:
2.1
通讯作者:
Suh, JW
Suh, JW
中科院分区:
生物学4区
文献类型:
--
作者:
Huh, JH;Kim, DJ;Suh, JW

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研究了S腺苷蛋氨酸对多种抗生素合成的影响,以确定在抗生素的生物合成途径中是否需要腺苷蛋氨酸依赖的甲基化。原始霉素依赖的甲基化IN和颗粒素在其生物合成途径中不需要依赖于SAM的甲基化,当低浓度(分别为50和10um)的SAM处理时,这两种抗生素的产量增加约2倍;相反,奥兰霉素和阿维菌素B1a在其生物合成中需要SAM作为甲基供体,在一定范围内,这两种抗生素的产量分别增加5倍和6倍。我们还发现,外源SAM处理可以激活途径特异性调控因子Gra-ORF9的转录。甲基转移酶抑制剂新诺菌素降低了奥兰霉素和阿维菌素B1a的产量,但同时加入SAM和新芬菌素可使这两种抗生素的产量恢复到对照水平。有趣的是,我们发现了S的甲基化产物同型半胱氨酸对这四个菌株的抗生素生产有类似的刺激作用。我们的结果清楚地表明,在链霉菌中使用SAM广泛激活了抗生素的生产。(C)2004年欧洲微生物学会联合会。爱思唯尔出版,版权所有。
The effect of S-adenosylmethionine (SAM) on the production of various antibiotics was investigated to determine whether SAM dpendent methylation is required in biosynthetic pathways of antibiotics. Pristinamycin dependent methylation IN 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 muM, 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-adeiiosylhomocysteine (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. (C) 2004 Federation of European Microbiological Societies. Published by Elsevier B.V. All rights reserved.