Structure, bioactivity, and resistance mechanism of streptomonomicin, an unusual lasso Peptide from an understudied halophilic actinomycete.
Structure, bioactivity, and resistance mechanism of streptomonomicin, an unusual lasso Peptide from an understudied halophilic actinomycete.
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DOI：
10.1016/j.chembiol.2014.11.017
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发表时间：
2015-02-19
影响因子：
--
通讯作者：
Mitchell DA
中科院分区：
文献类型：
--
作者：
Metelev M;Tietz JI;Melby JO;Blair PM;Zhu L;Livnat I;Severinov K;Mitchell DA
天然产物是药物开发中最重要的化合物来源。然而，与大规模筛选常见微生物生产者相关的化合物再发现率高得令人无法接受，这导致许多天然产物药物发现工作被放弃，尽管临床上有问题的抗生素耐药性越来越普遍。筛选未充分开发的类群是避免重新发现的一种策略。在此，我们报告的发现，分离，和结构解析的链霉素（STM），抗生素套索肽从白色链单孢菌，并报告其生产生物体的基因组。炭疽芽孢杆菌的STM抗性克隆具有walR突变，walR基因编码厚壁菌门中唯一已知的广泛分布和必需的双组分信号转导系统的反应调节剂。迄今为止，链单孢菌的生物合成和遗传特征不明，STM是该属中首次报道的化合物。我们的研究结果表明，未充分研究的微生物仍然是快速发现新型生物活性天然产物的富有成效的水库。
Natural products are the most historically significant source of compounds for drug development. However, unacceptably high rates of compound rediscovery associated with large-scale screening of common microbial producers have resulted in the abandonment of many natural product drug discovery efforts, despite the increasing prevalence of clinically-problematic antibiotic resistance. Screening of underexplored taxa represents one strategy to avoid rediscovery. Herein we report the discovery, isolation, and structural elucidation of streptomonomicin (STM), an antibiotic lasso peptide from Streptomonospora alba, and report the genome for its producing organism. STM-resistant clones of Bacillus anthracis harbor mutations to walR, the gene encoding a response regulator for the only known widely-distributed and essential two-component signal transduction system in Firmicutes. Streptomonospora had been hitherto biosynthetically and genetically uncharacterized, with STM being the first reported compound from the genus. Our results demonstrate that understudied microbes remain fruitful reservoirs for the rapid discovery of novel, bioactive natural products.
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影响因子：
14.9
作者：
Blin K;Medema MH;Kazempour D;Fischbach MA;Breitling R;Takano E;Weber T
通讯作者：
Weber T
影响因子：
--
作者：
Gavrish E;Sit CS;Cao S;Kandror O;Spoering A;Peoples A;Ling L;Fetterman A;Hughes D;Bissell A;Torrey H;Akopian T;Mueller A;Epstein S;Goldberg A;Clardy J;Lewis K
通讯作者：
Lewis K
影响因子：
15
作者：
Hegemann, Julian D.;Zimmermann, Marcel;Marahiel, Mohamed A.
通讯作者：
Marahiel, Mohamed A.
DOI：
10.1007/s10295-005-0077-9
发表时间：
2006-07-01
影响因子：
3.4
作者：
Baltz, Richard H.
通讯作者：
Baltz, Richard H.
影响因子：
3.2
作者：
Fukushima, Tatsuya;Afkham, Anahita;Sekiguchi, Junichi
通讯作者：
Sekiguchi, Junichi