Background

Saccharopolyspora erythraea (S. erythraea) is a Gram-positive bacterium widely used for the production of erythromycin, a potent macrolide antibiotic. However, the mechanism behind erythromycin production is poorly understood. In the high erythromycin-producer strain S. erythraea HL3168 E3, the level of copper ions positively correlates with erythromycin production. To explain this correlation, we performed a genome-based comparison between the wild-type strain NRRL23338 and the mutant strain HL3168 E3, and further characterized the identified gene(s) by targeted genome editing, mRNA transcript analysis, and functional analysis.

Results

The response regulator of the two-component system (TCS) encoded by the gene SACE_0101 in S. erythraea showed high similarity with CopR of TCS CopRS in Streptomyces coelicolor, which is involved in the regulation of copper metabolism. The deletion of SACE_0101 was beneficial for erythromycin synthesis most likely by causing changes in the intracellular copper homeostasis, leading to enhanced erythromycin production. In addition, Cu²⁺ supplementation and gene expression analysis suggested that SACE_0101 may be involved in the regulation of copper homeostasis and erythromycin production.

Conclusions

The mutation of SACE_0101 gene increased the yield of erythromycin, especially upon the addition of copper ions. Therefore, the two-component system gene SACE_0101 plays a crucial role in regulating copper homeostasis and erythromycin synthesis in S. erythraea.

中文翻译：

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两组分系统基因SACE_0101调节红糖酵母中的铜稳态

背景

糖多孢菌（S. erythraea）是革兰氏阳性细菌，广泛用于生产红霉素（一种有效的大环内酯类抗生素）。但是，对红霉素生产的机理了解甚少。在高红霉素生产菌菌株S.红霉素HL3168 E3，铜离子的水平正用红霉素生产相关。为了解释这种相关性，我们在野生型NRRL23338和突变型菌株HL3168 E3之间进行了基于基因组的比较，并通过靶向基因组编辑，mRNA转录本分析和功能分析进一步鉴定了所鉴定的基因。

结果

由该基因编码的双组分系统（TCS）的反应调节SACE_0101在S.红霉素表明具有高相似COPR TCS CopRS的在天蓝色链霉菌，其参与铜代谢的调节。SACE_0101的删除最有可能通过引起细胞内铜稳态的变化，从而导致红霉素生成的增加而对红霉素合成有益。另外，铜^2+的补充和基因表达分析表明SACE_0101可能参与铜稳态和红霉素生产的调节。

结论

SACE_0101基因的突变增加了红霉素的产量，特别是在添加铜离子后。因此，双组分体系基因SACE_0101在调节铜稳态和在红霉素合成至关重要的作用S.红霉素。