Abstract
BackgroundSaccharopolyspora 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.ResultsThe 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.ConclusionsThe 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.
Highlights
Saccharopolyspora erythraea is used mainly at an industrial scale to produce erythromycin, an important broadspectrum macrolide antibiotic used for industrial and clinical applications
We found that SACE_0101 plays a role in the regulation of copper homeostasis and that intracellular copper homeostasis is crucial for high erythromycin yield in the S. erythraea HL3168 E3 (E3) strain
Functional prediction of two-component system (TCS) SACE_0101/0102 We conducted a preliminary study on the function of TCS gene SACE_0101, a point mutant gene found in E3
Summary
Saccharopolyspora erythraea is used mainly at an industrial scale to produce erythromycin, an important broadspectrum macrolide antibiotic used for industrial and clinical applications. The mechanism on how S. erythraea produces high-yield erythromycin is poorly understood, hindering its rational optimization. In 2007, the genome of S. erythraea NRRL23338 was published providing the necessary resources to fully understand the mechanism of erythromycin synthesis. 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
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