A preliminary study of the mechanism of nitrate-stimulated remarkable increase of rifamycin production in Amycolatopsis mediterranei U32 by RNA-seq.
A preliminary study of the mechanism of nitrate-stimulated remarkable increase of rifamycin production in Amycolatopsis mediterranei U32 by RNA-seq.
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DOI：
10.1186/s12934-015-0264-y
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发表时间：
2015-06-04
影响因子：
6.4
通讯作者：
Wang J
中科院分区：
文献类型：
--
作者：
Shao ZH;Ren SX;Liu XQ;Xu J;Yan H;Zhao GP;Wang J
利福霉素是治疗结核分枝杆菌引起的传染病的重要抗生素。研究发现，在利福霉素SV的工业生产商地中海Amycolatopsis mediterranei U32中，在培养基中添加硝酸盐可显著提高利福霉素SV的产量。然而，这种硝酸盐介导的刺激的分子机制尚不清楚。本研究采用rna测序（RNA-seq）技术研究添加或不添加硝酸盐培养的U32细胞全基因组差异基因表达情况。在硝酸盐存在的情况下，U32保持了位于利福霉素生物合成簇和参与利福霉素前体生物合成的基因的高转录水平，包括3-氨基-5-二羟基苯甲酸、丙二酰辅酶a和(S)-甲基丙二酰辅酶a。然而，当培养基中不添加硝酸盐时，这些基因的转录在从对数中期过渡到早期稳定期期间急剧下降。有了这些认识，我们可以很容易地提出，硝酸盐通过增加前体供应和利福霉素生物合成酶来刺激利福霉素SV的产生。这是第一次在转录水平上彻底阐明硝酸盐介导的利福霉素刺激生产的机制，这可能有助于利福霉素SV的工业化生产，例如通过基于RNA-seq数据优化全球利福霉素生物合成途径。本文的在线版本（doi:10.1186/s12934-015-0264-y）包含补充材料，可供授权用户使用。
Rifamycin is an important antibiotic for the treatment of infectious disease caused by Mycobacteria tuberculosis. It was found that in Amycolatopsis mediterranei U32, an industrial producer for rifamycin SV, supplementation of nitrate into the medium remarkably stimulated the yield of rifamycin SV. However, the molecular mechanism of this nitrate-mediated stimulation remains unknown. In this study, RNA-sequencing (RNA-seq) technology was employed for investigation of the genome-wide differential gene expression in U32 cultured with or without nitrate supplementation. In the presence of nitrate, U32 maintained a high transcriptional level of genes both located in the rifamycin biosynthetic cluster and involved in the biosynthesis of rifamycin precursors, including 3-amino-5-dihydroxybenzoic acid, malonyl-CoA and (S)-methylmalonyl-CoA. However, when nitrate was omitted from the medium, the transcription of these genes declined sharply during the transition from the mid-logarithmic phase to the early stationary phase. With these understandings, one may easily propose that nitrate stimulates the rifamycin SV production through increasing both the precursors supply and the enzymes for rifamycin biosynthesis. It is the first time to thoroughly illustrate the mechanism of the nitrate-mediated stimulation of rifamycin production at the transcriptional level, which may facilitate improvement of the industrial production of rifamycin SV, e.g. through optimizing the global rifamycin biosynthetic pathways on the basis of RNA-seq data. The online version of this article (doi:10.1186/s12934-015-0264-y) contains supplementary material, which is available to authorized users.
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DOI：
10.1093/bioinformatics/btq033
发表时间：
2010-03-15
期刊：
Bioinformatics (Oxford, England)
影响因子：
--
作者：
Quinlan AR;Hall IM
通讯作者：
Hall IM
影响因子：
48
作者：
Langmead, Ben;Salzberg, Steven L.
通讯作者：
Salzberg, Steven L.
DOI：
10.1099/00221287-139-8-1773
发表时间：
1993-08-01
期刊：
JOURNAL OF GENERAL MICROBIOLOGY
影响因子：
--
作者：
HILLEMANN, D;DAMMANN, T;WOHLLEBEN, W
通讯作者：
WOHLLEBEN, W
影响因子：
2.9
作者：
Meier, TW;Thoma, NH;Leadlay, PF
通讯作者：
Leadlay, PF
影响因子：
14.9
作者：
McClure R;Balasubramanian D;Sun Y;Bobrovskyy M;Sumby P;Genco CA;Vanderpool CK;Tjaden B
通讯作者：
Tjaden B