Multi-Omics Analysis of the Effect of cAMP on Actinorhodin Production in Streptomyces coelicolor.
Multi-Omics Analysis of the Effect of cAMP on Actinorhodin Production in Streptomyces coelicolor.
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cAMP对天蓝色链霉菌放线菌紫素合成影响的多组学分析
DOI：
10.3389/fbioe.2020.595552
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发表时间：
2020
影响因子：
5.7
通讯作者：
Fukusaki E
中科院分区：
文献类型：
--
作者：
Nitta K;Carratore FD;Breitling R;Takano E;Putri SP;Fukusaki E
环磷酸腺苷（cAMP）在天蓝色链霉菌的形态发育和抗生素产生中起着重要的调控作用。然而，cAMP水平和抗生素产生之间的功能联系以及cAMP调节抗生素产生的机制仍不清楚。本研究采用代谢组学和转录组学相结合的多组学分析方法，对S。coelicolor菌株产生次级代谢产物放线菌紫素（Act）或缺乏大多数次级代谢产物生物合成途径，包括Act。比较多组学分析的两个菌株显示，细胞内和细胞外cAMP丰度与放线菌紫素生产强烈相关。值得注意的是，补充cAMP改善了细胞生长和抗生素生产。对补充cAMP的S.腔肠培养物显示鸟嘌呤和嘌呤代谢基因的表达水平增加。基于这种现象，进行补充7-甲基鸟嘌呤（利用鸟嘌呤的反应的竞争性抑制剂），有或没有额外的cAMP补充。该实验表明，7-甲基鸟嘌呤抑制的反应介导了对生长和抗生素产生的积极作用，这可能发生在cAMP补充的下游。
Cyclic adenosine monophosphate (cAMP) has been known to play an important role in regulating morphological development and antibiotic production in Streptomyces coelicolor. However, the functional connection between cAMP levels and antibiotic production and the mechanism by which cAMP regulates antibiotic production remain unclear. In this study, metabolomics- and transcriptomics-based multi-omics analysis was applied to S. coelicolor strains that either produce the secondary metabolite actinorhodin (Act) or lack most secondary metabolite biosynthesis pathways including Act. Comparative multi-omics analysis of the two strains revealed that intracellular and extracellular cAMP abundance was strongly correlated with actinorhodin production. Notably, supplementation of cAMP improved cell growth and antibiotic production. Further multi-omics analysis of cAMP-supplemented S. coelicolor cultures showed an increase of guanine and the expression level of purine metabolism genes. Based on this phenomenon, supplementation with 7-methylguanine, a competitive inhibitor of reactions utilizing guanine, with or without additional cAMP supplementation, was performed. This experiment revealed that the reactions inhibited by 7-methylguanine are mediating the positive effect on growth and antibiotic production, which may occur downstream of cAMP supplementation.