Please wait a minute...

中国生物工程杂志

CHINA BIOTECHNOLOGY
中国生物工程杂志
中国生物工程杂志  2015, Vol. 35 Issue (9): 105-113    DOI: 10.13523/j.cb.20150915
综述     
无机磷酸盐对链霉菌合成次级代谢产物的影响
尹守亮1,2, 张玉秀1, 张琪1, 豆梦楠1, 杨克迁2
1. 中国矿业大学化学与环境工程学院 北京 100083;
2 中国科学院微生物研究所 微生物资源前期开发国家重点实验室 北京 100101
The Effect of Inorganic Phosphate on the Biosynthesis of Secondary Metabolites in Streptomyces
YIN Shou-liang1,2, ZHANG Yu-xiu1, ZHANG Qi1, DOU Meng-nan1, YANG Ke-qian2
1 Department of Environmental and Biological Engineering, School of Chemical and Environmental Engineering, China University of Mining and Technology, Beijing 100083, China;
2 State Key Laboratory of Microbial Resources, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China
 全文: PDF(572 KB)   HTML
摘要：

链霉菌一个突出的特征是具有合成丰富的次级代谢产物的能力,许多次级代谢产物,如抗生素、免疫抑制剂、抗癌物质等在临床医药、水产养殖业等领域具有重要的应用价值.链霉菌次级代谢产物的合成常与环境中的营养因子有着密切的关系,在代谢水平上综述了无机磷酸盐对链霉菌合成次级代谢产物的影响,并在转录水平上阐释了双组分信号转导系统PhoR-PhoP的分子调控机制.PhoR-PhoP能够感应环境中的无机磷酸盐信号,当无机磷酸盐的浓度低于一定"阈值"时,PhoP蛋白作为主导的调控因子将抑制参与中心代谢和次级代谢等一系列基因的转录表达,减慢磷酸盐的消耗,并激活磷酸盐的摄取和转运系统及时补充胞内的磷酸盐,最终影响链霉菌次级代谢产物的合成和形态发育分化.
关键词： 次级代谢产物;  无机磷酸盐;  PhoR-PhoP双组分信号转导系统;  分子调控机制    
Abstract:

Streptomyces are well known as a particularly abundant source of secondary metabolites, including antibiotics, immunosuppressants, anti-cancer agents and many other bioactive compounds. Many of them have important application in the field of clinical medicine and aquaculture, etc. Nevertheless, the synthesis of secondary metabolites is often closely related with environmental and nutritional factors. Herein,the influence of inorganic phosphate and the molecular mechanism of the two-component PhoR-PhoP signal transduction system on the synthesis of secondary metabolites are reviewed. Streptomycetes sense and respond to phosphate via the two-component PhoR-PhoP signal transduction system.When the concentration of phosphate in the environments decreases below a threshold level. PhoP plays a major role in the repression of the central and secondary metabolic pathways to slow down the consumption of phosphate, and the activation of scavenging uptake and transport systems that allow the cell to recover inorganic phosphate from external sources, which ultimately affect the secondary metabolites production and morphological differentiation.
Key words: Secondary metabolites    Inorganic phosphate    The two-component PhoR-PhoP signal transduction system    Molecular mechanism
收稿日期: 2015-04-14 出版日期: 2015-09-25
ZTFLH:  Q582  
基金资助:

国家自然科学基金(31130001),中国矿业大学(北京)中央高校基本科研业务费专项基金(2010YH05)资助项目
通讯作者: 张玉秀, 杨克迁     E-mail: zhangyuxiu@cumtb.edu.cn;yangkq@im.ac.cn
服务　　
把本文推荐给朋友
加入引用管理器
E-mail Alert
RSS
作者相关文章　　

引用本文:

尹守亮, 张玉秀, 张琪, 豆梦楠, 杨克迁. 无机磷酸盐对链霉菌合成次级代谢产物的影响[J]. 中国生物工程杂志, 2015, 35(9): 105-113.

YIN Shou-liang, ZHANG Yu-xiu, ZHANG Qi, DOU Meng-nan, YANG Ke-qian. The Effect of Inorganic Phosphate on the Biosynthesis of Secondary Metabolites in Streptomyces. China Biotechnology, 2015, 35(9): 105-113.

链接本文:

https://manu60.magtech.com.cn/biotech/CN/10.13523/j.cb.20150915    或    https://manu60.magtech.com.cn/biotech/CN/Y2015/V35/I9/105


[1] Challis G L, Hopwood D A. Synergy and contingency as driving forces for the evolution of multiple secondary metabolite production by Streptomyces species. Proceedings of the National Academy of Sciences of the United States of America, 2003,100 (Suppl 2):14555-14561.

[2] 尹守亮, 常亚婧, 邓苏萍,等. 以病原菌群体感应系统为靶标的新型抗菌药物的研究进展. 药学学报, 2011,46(6):613-621. Yin S L, Chang Y J, Deng S P, et al. Research progress of new antibacterial drugs that target bacterial quorum sensing systems. Acta Pharmaceutica Sinica, 2011,46(6):613-621.

[3] Robbers J E, Robertson L W, Hornemann K M, et al. Physiological studies on ergot: further studies on the induction of alkaloid synthesis by tryptophan and its inhibition by phosphate. J Bacteriol, 1972,112(2):791-796.

[4] Rodriguez-Ortiz R, Mehta B J, Avalos J, et al. Stimulation of bikaverin production by sucrose and by salt starvation in Fusarium fujikuroi. Appl Microbiol Biotechnol, 2010,85(6):1991-2000.

[5] 王琳淇, 谭华荣. 微生物次生代谢的分子调控. 微生物学报, 2009,49(4):411-416. Wang L Q, Tan H R. Molecular regulation of microbial secondary metabolites. Acta Microbiologica Sinica,2009,49(4):411-416.

[6] Niu G, Tan H. Biosynthesis and regulation of secondary metabolites in microorganisms. Science China Life Sciences, 2013,56(7):581-583.

[7] Liras P, Asturias J A, Martin J F. Phosphate control sequences involved in transcriptional regulation of antibiotic biosynthesis. Trends in Biotechnology, 1990,8(7):184-189.

[8] Martin J F, Liras P, Demain A L. ATP and adenylate energy charge during phosphate-mediated control of antibiotic synthesis. Biochem Biophys Res Commun, 1978,83(3):822-828.

[9] Hanel F, Krugel H, Fiedler G. Arsenical resistance of growth and phosphate control of antibiotic biosynthesis in Streptomyces. J Gen Microbiol, 1989,135(3):583-591.

[10] Martin J F, Demain A L. Control of antibiotic biosynthesis. Microbiological Reviews, 1980,44(2):230-251.

[11] Martín J F. Control of antibiotic synthesis by phosphate. Advances in Biochemical Engineering, 1977,6(1):105-127.

[12] Mertz F P, Doolin L E. The effect of inorganic phosphate on the biosynthesis of vancomycin. Can J Microbiol, 1973,19(2):263-270.

[13] McDowall K J, Thamchaipenet A, Hunter I S. Phosphate control of oxytetracycline production by Streptomyces rimosus is at the level of transcription from promoters overlapped by tandem repeats similar to those of the DNA-binding sites of the OmpR family. J Bacteriol, 1999,181(10):3025-3032.

[14] Perlman D, Wagman G H. Studies on the utilization of lipids by streptomyces griseus. J Bacteriol, 1952,63(2):253-262.

[15] Hostalek Z. Relationship between the carbohydrate metabolism of Streptomyces aureofaciens and the biosynthesis of chlortetracycline. I. The effect of interrupted aeration, inorganic phosphate and benzyl thiocyanate on chlortetracycline biosynthesis. Folia Microbiol (Praha), 1964,18(4):78-88.

[16] Walker M S, Walker J B. Streptomycin biosynthesis and metabolism. Enzymatic phosphorylation of dihydrostreptobiosamine moieties of dihydro-streptomycin-(streptidino) phosphate and dihydrostreptomycin by Streptomyces extracts. J Biol Chem, 1970,245(24):6683-6689.

[17] Miller A L, Walker J B. Enzymatic phosphorylation of streptomycin by extracts of streptomycin-producing strains of Streptomyces. J Bacteriol, 1969,99(2):401-405.

[18] Meza G, Barba-Behrens N, Granados O, et al. Vestibular histofluorescence could be due to accumulation of both the antibiotic and its derivative, streptidine, after acute streptomycin treatment in the guinea pig. Histology and Histopathology, 2001,16(4):1143-1148.

[19] Bandyopadhyay S K, Majumdar S K. Regulation of the formation of alkaline phosphatase during neomycin biosynthesis. Antimicrob Agents Chemother, 1974,5(4):431-434.

[20] Vorisek J, Powell A J, Vanek Z. Regulation of biosynthesis of secondary metabolites. 13. Specific allosteric properties of phosphoenolpyruvate carboxylase in Streptomyces aureofaciens. Folia Microbiol (Praha), 1970,15(3):153-159.

[21] Byun S M, Jenness R, Ridley W P, et al. The stereospecificity of D-glucose-6-phosphate: 1L-myo-inositol-1-phosphate cycloaldolase on the hydrogen atoms at C-6. Biochem Biophys Res Commun, 1973,54(3):961-967.

[22] Loewus M W, Loewus F. D-glucose 6-phosphate cycloaldolase: Inhibition studies and aldolase function. Plant Physiology, 1973,51(2):263-266.

[23] Harold F M. Inorganic polyphosphates in biology: structure, metabolism, and function. Bacteriological Reviews, 1966,30(4):772-794.

[24] Allenby N E, Laing E, Bucca G, et al. Diverse control of metabolism and other cellular processes in Streptomyces coelicolor by the PhoP transcription factor: genome-wide identification of in vivo targets. Nucleic Acids Research, 2012,40(19):9543-9556.

[25] Sola-Landa A, Moura R S, Martin J F. The two-component PhoR-PhoP system controls both primary metabolism and secondary metabolite biosynthesis in Streptomyces lividans. Proceedings of the National Academy of Sciences of the United States of America, 2003,100(10):6133-6138.

[26] Willett J W, Tiwari N, Muller S, et al. Specificity residues determine binding affinity for two-component signal transduction systems. MBio, 2013,4(6):e00420-00413.

[27] Pirrung M C. Histidine kinases and two-component signal transduction systems. Chem Biol, 1999,6(6):167-175.

[28] Stock J B, Ninfa A J, Stock A M. Protein phosphorylation and regulation of adaptive responses in bacteria. Microbiological Reviews, 1989,53(4):450-490.

[29] Tseng H C, Chen C W. A cloned ompR-like gene of Streptomyces lividans 66 suppresses defective melC1, a putative copper-transfer gene. Mol Microbiol, 1991,5(5):1187-1196.

[30] Sola-Landa A, Rodriguez-Garcia A, Apel A K, et al. Target genes and structure of the direct repeats in the DNA-binding sequences of the response regulator PhoP in Streptomyces coelicolor. Nucleic Acids Research, 2008,36(4):1358-1368.

[31] Sola-Landa A, Rodriguez-Garcia A, Franco-Dominguez E, et al. Binding of PhoP to promoters of phosphate-regulated genes in Streptomyces coelicolor: identification of PHO boxes. Mol Microbiol, 2005,56(5):1373-1385.

[32] Apel A K, Sola-Landa A, Rodriguez-Garcia A, et al. Phosphate control of phoA, phoC and phoD gene expression in Streptomyces coelicolor reveals significant differences in binding of PhoP to their promoter regions. Microbiology, 2007,153(10):3527-3537.

[33] Mendes M V, Tunca S, Anton N, et al. The two-component phoR-phoP system of Streptomyces natalensis: Inactivation or deletion of phoP reduces the negative phosphate regulation of pimaricin biosynthesis. Metabolic Engineering, 2007,9(2):217-227.

[34] Santos-Beneit F, Rodriguez-Garcia A, Sola-Landa A, et al. Cross-talk between two global regulators in Streptomyces: PhoP and AfsR interact in the control of afsS, pstS and phoR Ptranscription. Mol Microbiol, 2009,72(1):53-68.

[35] Uguru G C, Stephens K E, Stead J A, et al. Transcriptional activation of the pathway-specific regulator of the actinorhodin biosynthetic genes in Streptomyces coelicolor. Mol Microbiol, 2005,58(1):131-150.

[36] D'Alia D, Eggle D, Nieselt K, et al. Deletion of the signalling molecule synthase ScbA has pleiotropic effects on secondary metabolite biosynthesis, morphological differentiation and primary metabolism in Streptomyces coelicolor A3(2). Microbial Biotechnology, 2011,4(2):239-251.

[37] Rodriguez-Garcia A, Barreiro C, Santos-Beneit F, et al. Genome-wide transcriptomic and proteomic analysis of the primary response to phosphate limitation in Streptomyces coelicolor M145 and in a Deltapho Pmutant. Proteomics, 2007,7(14):2410-2429.

[38] Liu W, Eder S, Hulett F M. Analysis of Bacillus subtilistagAB and tagDEF expression during phosphate starvation identifies a repressor role for PhoP-P. J Bacteriol, 1998,180(3):753-758.

[39] Diaz M, Esteban A, Fernandez-Abalos J M, et al. The high-affinity phosphate-binding protein PstS is accumulated under high fructose concentrations and mutation of the corresponding gene affects differentiation in Streptomyces lividans. Microbiology, 2005,151(8):2583-2592.

[40] Santos-Beneit F, Rodriguez-Garcia A, Franco-Dominguez E, et al. Phosphate-dependent regulation of the low- and high-affinity transport systems in the model actinomycete Streptomyces coelicolor. Microbiology, 2008,154(8):2356-2370.

[41] Rodriguez-Garcia A, Sola-Landa A, Apel K, et al. Phosphate control over nitrogen metabolism in Streptomyces coelicolor: direct and indirect negative control of glnR, glnA, glnII and amtB expression by the response regulator PhoP. Nucleic Acids Research, 2009,37(10):3230-3242.

[42] Den Hengst C D, Tran N T, Bibb M J, et al. Genes essential for morphological development and antibiotic production in Streptomyces coelicolor are targets of BldD during vegetative growth. Mol Microbiol, 2010,78(2):361-379.

[43] Santos-Beneit F, Barriuso-Iglesias M, Fernandez-Martinez L T, et al. The RNA polymerase omega factor RpoZ is regulated by PhoP and has an important role in antibiotic biosynthesis and morphological differentiation in Streptomyces coelicolor. Appl Environ Microbiol, 2011,77(21):7586-7594.

[44] Gehring A M, Yoo N J, Losick R. RNA polymerase sigma factor that blocks morphological differentiation by Streptomyces coelicolor. J Bacteriol, 2001,183(20):5991-5996.

[45] Tanaka A, Takano Y, Ohnishi Y, et al. AfsR recruits RNA polymerase to the afsS promoter: a model for transcriptional activation by SARPs. J Mol Biol, 2007,369(2):322-333.

[46] Lee P C, Umeyama T, Horinouchi S. afsS is a target of AfsR, a transcriptional factor with ATPase activity that globally controls secondary metabolism in Streptomyces coelicolor A3(2). Mol Microbiol, 2002,43(6):1413-1430.

[47] Floriano B, Bibb M. afsR is a pleiotropic but conditionally required regulatory gene for antibiotic production in Streptomyces coelicolor A3(2). Mol Microbiol, 1996,21(2):385-396.

[48] Santos-Beneit F, Rodriguez-Garcia A, Martin J F. Complex transcriptional control of the antibiotic regulator afsS in Streptomyces: PhoP and AfsR are overlapping, competitive activators. J Bacteriol, 2011,193(9):2242-2251.

[49] 李宜鸿, 李珊珊, 艾国民,等. 天蓝色链霉菌代谢物组测定方法优化及其代谢特征. 生物工程学报, 2014,30(4):554-568. Li Y H, Li S S, Ai G M, et al. Optimized sample preparation for metabolome studies on Streptomyces coelicolor. Chinese Journal of Biotechnology, 2014,30(4):554-568.

[50] Wang W, Ji J, Li X, et al. Angucyclines as signals modulate the behaviors of Streptomyces coelicolor. Proceedings of the National Academy of Sciences of the United States of America, 2014,111(15):5688-5693.
[1] 李晓梅, 林春燕, 逄爱萍, 李晓波, 赵广荣. 合成生物学在链霉菌次级代谢产物研发中的应用[J]. 中国生物工程杂志, 2015, 35(4): 92-97.
[2] 杨毅, 李治, 高玲霞, 孙燕. 荧光假单胞菌抗生性代谢产物合成相关基因的研究现状[J]. 中国生物工程杂志, 2012, 32(08): 100-106.
主管：中国科学院 　主办：中国科学院文献情报中心 　中国生物技术发展中心 　中国生物工程学会