Multi-omics Study of Planobispora rosea, Producer of the Thiopeptide Antibiotic GE2270A.
Multi-omics Study of Planobispora rosea, Producer of the Thiopeptide Antibiotic GE2270A.
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DOI：
10.1128/msystems.00341-21
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发表时间：
2021-06-29
期刊：
影响因子：
6.4
通讯作者：
Takano E
中科院分区：
文献类型：
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作者：
Del Carratore F;Iorio M;Pérez-Bonilla M;Schmidt K;Pérez-Redondo R;Sosio M;Macdonald SJ;Gyulev IS;Tsigkinopoulou A;Thomas GH;Genilloud O;Rodríguez-García A;Donadio S;Breitling R;Takano E
玫瑰Planobispora是强效硫肽抗生素GE2270A的天然生产者。在这里，我们展示了在GE2270A生产过程中玫瑰玫瑰的代谢组学和转录组学分析结果。所产生的数据为这种遗传上难缠的细菌的生物学提供了有用的见解。我们描述了与指数生长阶段结束相关的蛋白质生物合成和呼吸链关闭的细节。我们也提供了第一个描述的磷酸盐调控在玫瑰。基于转录组学数据，我们表明在我们的实验条件下，磷酸盐和铁都限制了玫瑰玫瑰的生长。此外，我们还鉴定并验证了一个新的生物合成基因簇，该基因簇与玫瑰中铁载体benarthin和dibenarthin的生产有关。同时，代谢组学和转录组学数据被用于告知和完善玫瑰玫瑰的第一个基因组尺度的代谢模型，这将是一个有价值的框架，用于解释这个有趣但特征不明显的物种的生物学未来研究。玫瑰Planobispora rosea是一种遗传上难以处理的细菌，用于工业规模上生产GE2270A。GE2270A是一种有效的硫肽抗生素，目前用作合成治疗艰难梭菌感染和痤疮的两种化合物的前体，正在临床研究中。在这里，我们提出了这个重要的细菌的第一个系统的多组学研究，这提供了一个急需的详细的图片，代谢动力学的玫瑰玫瑰在生产GE2270A。作者视频：本文的作者视频摘要是可用的。
Planobispora rosea is the natural producer of the potent thiopeptide antibiotic GE2270A. Here, we present the results of a metabolomics and transcriptomics analysis of P. rosea during production of GE2270A. The data generated provides useful insights into the biology of this genetically intractable bacterium. We characterize the details of the shutdown of protein biosynthesis and the respiratory chain associated with the end of the exponential growth phase. We also provide the first description of the phosphate regulon in P. rosea. Based on the transcriptomics data, we show that both phosphate and iron are limiting P. rosea growth in our experimental conditions. Additionally, we identified and validated a new biosynthetic gene cluster associated with the production of the siderophores benarthin and dibenarthin in P. rosea. Together, the metabolomics and transcriptomics data are used to inform and refine the very first genome-scale metabolic model for P. rosea, which will be a valuable framework for the interpretation of future studies of the biology of this interesting but poorly characterized species. IMPORTANCE Planobispora rosea is a genetically intractable bacterium used for the production of GE2270A on an industrial scale. GE2270A is a potent thiopeptide antibiotic currently used as a precursor for the synthesis of two compounds under clinical studies for the treatment of Clostridium difficile infection and acne. Here, we present the very first systematic multi-omics investigation of this important bacterium, which provides a much-needed detailed picture of the dynamics of metabolism of P. rosea while producing GE2270A. Author Video: An author video summary of this article is available.