The Link between Purine Metabolism and Production of Antibiotics in Streptomyces
The Link between Purine Metabolism and Production of Antibiotics in Streptomyces
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DOI：
10.3390/antibiotics8020076
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发表时间：
2019-06
期刊：
影响因子：
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通讯作者：
Smitha Sivapragasam;A. Grove
中科院分区：
文献类型：
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作者：
Smitha Sivapragasam;A. Grove
压力和饥饿会导致细菌细胞激活严格的反应。这导致与生长相关的能量需求过程下调，以及与生存和应激反应相关的基因上调。四磷酸和五磷酸鸟苷（统称为 (p)ppGpp）对此过程至关重要。在革兰氏阳性细菌中，(p)ppGpp 的主要功能是限制 GTP 的细胞水平，其后果之一是需要 GTP 作为起始核苷酸的基因（例如 rRNA 基因）的转录减少。在链霉菌中，严格的反应还与复杂的形态分化和次级代谢产物（包括抗生素）的产生有关。这些过程也受到第二信使 c-di-GMP 的影响。由于 GTP 是 (p)ppGpp 和 c-di-GMP 的底物，因此需要对细胞 GTP 水平进行精细调节，以确保这些鸟苷衍生物的充分合成。在这里，我们讨论控制鸟苷代谢的机制以及它们如何影响链霉菌属抗生素的生产。
Stress and starvation causes bacterial cells to activate the stringent response. This results in down-regulation of energy-requiring processes related to growth, as well as an upregulation of genes associated with survival and stress responses. Guanosine tetra- and pentaphosphates (collectively referred to as (p)ppGpp) are critical for this process. In Gram-positive bacteria, a main function of (p)ppGpp is to limit cellular levels of GTP, one consequence of which is reduced transcription of genes that require GTP as the initiating nucleotide, such as rRNA genes. In Streptomycetes, the stringent response is also linked to complex morphological differentiation and to production of secondary metabolites, including antibiotics. These processes are also influenced by the second messenger c-di-GMP. Since GTP is a substrate for both (p)ppGpp and c-di-GMP, a finely tuned regulation of cellular GTP levels is required to ensure adequate synthesis of these guanosine derivatives. Here, we discuss mechanisms that operate to control guanosine metabolism and how they impinge on the production of antibiotics in Streptomyces species.