Global and pathway-specific transcriptional regulations of pactamycin biosynthesis in Streptomyces pactum.
Global and pathway-specific transcriptional regulations of pactamycin biosynthesis in Streptomyces pactum.
复制标题
DOI：
10.1007/s00253-018-9375-9
复制
发表时间：
2018-12
影响因子：
5
通讯作者：
Mahmud T
中科院分区：
文献类型：
--
作者：
Lu W;Alanzi AR;Abugrain ME;Ito T;Mahmud T
从链霉菌中分离得到的一种结构独特的氨基环醇类天然产物，具有很强的抗菌、抗肿瘤和抗原生动物活性。然而，在目前使用的培养条件下，其产量通常较低。目的了解抑霉素生物合成的调控机制，探索提高抑霉素产量的可能性。pactum，我们研究了帕塔霉素生物合成的转录调控。在体内灭活两个假定的途径特异性调控基因，ptmE和ptmF，导致突变株不能产生帕塔霉素。使用包含整合到S. pactum染色体挽救了pactamycin的生产。ΔptmE和ΔptmF菌株的转录分析表明，这两个基因控制整个紫杉霉素生物合成基因簇的表达。然而，试图通过在S. Pactum不能提高帕他霉素的产率。我们发现，帕塔霉素的生物合成是敏感的磷酸调节。无机磷酸盐的浓度高于2 mM时，生物合成基因的转录和抗生素的产生都消失了。S. Pactum和生物信息学研究揭示了全局调节基因的存在，例如，编码双组分PhoR-PhoP系统的基因，通常参与次级代谢。phoP的失活对帕他霉素的产量没有明显影响。然而，在phoP：：aac（3）IV突变体中，帕塔霉素生物合成不受外部无机磷酸盐浓度的影响。
Pactamycin, a structurally unique aminocyclitol natural product isolated from Streptomyces pactum, has potent antibacterial, anti-tumor and anti-protozoa activities. However, its production yields under currently used culture conditions are generally low. To understand how pactamycin biosynthesis is regulated and explore the possibility of improving pactamycin production in S. pactum, we investigated the transcription regulations of pactamycin biosynthesis. In vivo inactivation of two putative pathway-specific regulatory genes, ptmE and ptmF, resulted in mutant strains that are not able to produce pactamycin. Genetic complementation using a cassette containing ptmE and ptmF integrated into the S. pactum chromosome rescued the production of pactamycin. Transcriptional analysis of the ΔptmE and ΔptmF strains suggests that both genes control the expression of the whole pactamycin biosynthetic gene cluster. However, attempts to overexpress these regulatory genes by introducing a second copy of the genes in S. pactum did not improve the production yield of pactamycin. We discovered that pactamycin biosynthesis is sensitive to phosphate regulation. Concentration of inorganic phosphate higher than 2 mM abolished both the transcription of the biosynthetic genes and the production of the antibiotic. Draft genome sequencing of S. pactum and bioinformatics studies revealed the existence of global regulatory genes, e.g., genes that encode a two-component PhoR-PhoP system, which are commonly involved in secondary metabolism. Inactivation of phoP did not show any significant effect to pactamycin production. However, in the phoP::aac(3)IV mutant, pactamycin biosynthesis is not affected by external inorganic phosphate concentration.
登录
查看更多内容
影响因子：
--
作者：
Lu, Wanli;Roongsawang, Niran;Mahmud, Taifo
通讯作者：
Mahmud, Taifo
影响因子：
3.6
作者：
Li, Rui;Liu, Gang;Tan, Huarong
通讯作者：
Tan, Huarong
影响因子：
3.1
作者：
Fernandez-Martinez, Lorena T.;Santos-Beneit, Fernando;Martin, Juan F.
通讯作者：
Martin, Juan F.
DOI：
10.1128/aem.10.4.302-304.1962
发表时间：
1962-01-01
期刊：
APPLIED MICROBIOLOGY
影响因子：
--
作者：
BHUYAN, BK
通讯作者：
BHUYAN, BK
影响因子：
3.3
作者：
Iwatsuki, Masato;Nishihara-Tsukashima, Aki;Omura, Satoshi
通讯作者：
Omura, Satoshi