Generation and study of the strains of streptomycetes - heterologous hosts for production of moenomycin.
Generation and study of the strains of streptomycetes - heterologous hosts for production of moenomycin.
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DOI：
10.1134/s1022795414040085
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发表时间：
2014-04
影响因子：
0.6
通讯作者：
Fedorenko V
中科院分区：
文献类型：
--
作者：
Lopatniuk M;Ostash B;Luzhetskyy A;Walker S;Fedorenko V
莫诺霉素（Mm）是一类磷酸糖脂类天然产物，被认为是开发新型抗生素的蓝图。天然的Mm生产者，加纳链霉菌（ATCC14672），产生非常少量的莫诺霉素，促进了对遗传方法的研究，以提高其滴度。异源表达莫诺霉素生物合成基因簇（moe）将是实现这一目标的途径之一。在这里，我们报道了一些产生nosokomycin A2 （Mm家族成员之一）的新型异源链霉菌宿主的产生，并确定了它们生产抗生素的潜力。链霉菌遗传模型菌株S. coelicolor（菌株M1152）的rpoB点突变比亲本菌株M145和M512显著提高了nosokomycin A2的产量，而同一种菌株M1154的双rpoBrpsL突变则降低了nosokomycin A2的产量。我们的研究结果指出了以前未预料到的突变之间的上位相互作用，这些突变单独已知对抗生素生产非常有益。我们还首次发现兼性化养链霉菌S. thermospinosisporus和氯霉素产生菌S. venezuela可以作为更多基因的宿主。
Moenomycins (Mm) are family of phosphoglycolipid natural products that is considered a blueprint to develop new class of antibiotics. The natural Mm producer, Streptomyces ghanaensis (ATCC14672), produces very low amounts of moenomycin, fueling the investigations on genetic approaches to improve its titers. Heterologous expression of moenomycin biosynthesis gene cluster (moe) would be one of the ways to reach this goal. Here we report the generation of a number of novel heterologous streptomycete hosts producing nosokomycin A2 (one of the members of Mm family), and determine their potential for the antibiotic production. The rpoB point mutation in the model strain of Streptomyces genetics, S. coelicolor (strain M1152) significantly improved nosokomycin A2 production compared to parental strains (M145 and M512), while double rpoBrpsL mutation in the same species (strain M1154) decreased it. Our results point to the previously unanticipated epistatic interactions between mutations that individually are known to be highly beneficial for antibiotic production. We also showed here for the first time that facultative chemolitotrophic streptomycete S. thermospinosisporus and chloramphenicol producer S. venezuelae can be used as the hosts for moe genes.