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中国生物工程杂志

China Biotechnology
China Biotechnology  2015, Vol. 35 Issue (9): 122-127    DOI: 10.13523/j.cb.20150917
    
Metabolic Control Fermentation Mechanism and Breeding Strategies of Cytidine Excessive Biosynthesis in Bacillus amyloliquefaciens
WU Qing, LIU Hui-yan, FANG Hai-tian, HE Jian-guo, HE Xiao-guang, YU Li-nan, WANG Meng-jiao
School of Agriculture Ningxia University, Yinchuan 750021, China
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Abstract  

Cytidine is good intermediates of anti-tumor and antiviral, also can be used as health food ingredients.The metabolic regulatory mechanism of cytidine biosynthesis in Bacillus amyloliquefaciens was discussed and the breeding strategy of constructing cytidine high-yielding strain was summarized. The focuses were on elaborating the six breeding strategies, such as improving the pyrimidine operon transcriptional level of Bacillus amyloliquefaciens, enhancing cytidine anabolic pathways and central metabolic pathways to cytidine synthesis, blocking degradation pathway of cytidine, increasing the pentose phosphate pathway to the sub-flow of cytidine synthesis pathway, reducing the bypass pathway and accelerating cytidine secretion.Thereby, the strategies of breeding high yield strain were proposed, which could provide some ideas for breeding cytidine high-yielding strains, and solve the existing problems in the processing of cytidine industrial production.



Key wordsBacillus amyloliquefaciens      Cytidine      Metabolic regulation mechanism      Breeding strategy     
Received: 25 March 2015      Published: 25 September 2015
ZTFLH:  Q819  
Cite this article:

WU Qing, LIU Hui-yan, FANG Hai-tian, HE Jian-guo, HE Xiao-guang, YU Li-nan, WANG Meng-jiao. Metabolic Control Fermentation Mechanism and Breeding Strategies of Cytidine Excessive Biosynthesis in Bacillus amyloliquefaciens. China Biotechnology, 2015, 35(9): 122-127.

URL:

https://manu60.magtech.com.cn/biotech/10.13523/j.cb.20150917     OR     https://manu60.magtech.com.cn/biotech/Y2015/V35/I9/122


[1] 姜妍, 许爱军. 国内外抗病毒药物研发进展. 黑龙江医药, 2006, 19(5): 388-392. Jiang Y, Xu A J. International research progress of the Antiviral. Heilongjiang Medicine Journal, 2006, 19(5):388-392.

[2] 乔宾福. 微生物产生核苷和核酸. 工业微生物, 1998, 28(1): 22-27. Qiao B F. Microbial production of nucleotides and nucleic acids. Industrial Microorganism, 1998, 28(1): 22-27.

[3] 怀丽华, 陈宁. 嘧啶核苷高产菌的代谢控制育种策略. 食品与发酵工业, 2005, 31(10): 107-110. Huai L H, Chen N. The metabolic control strategy for breeding of pyrimidine high-producing strain. Food and Fermentation Industries, 2005, 31(10): 107-110.

[4] Liu Shijie. Evolution and Genetic Engineering. 4th ed. Bioprocess Engineering, 2013.695-741.

[5] 张蓓. 代谢工程. 天津: 天津科技大学出版社, 2003.90-113. Zhang B. Metabolic Engineering. Tianjin: Tianjin University Press, 2003.90-113.

[6] 王锐. 嘧啶核苷的研究进展. 生物技术通讯, 2007, 18(3): 539-542. Wang R. Advances in pyrimidine. Letters in Biotechnology, 2007,18(3): 539-542.

[7] 孙占敏, 张克旭, 陈宁. 胞苷产生菌的选育. 现代食品科技, 2007, 22 (3): 284-285. Sun Z M, Zhang K X, Chen N. Breeding Bacillus subtilis mutants producing cytidine. Modern Food Science and Technology, 2007, 22 (3): 284-285.

[8] 盛春雷, 丁庆豹, 丁翠敏, 等. 胞苷生产菌的选育. 生物技术, 2007, 17(5): 57-59. Sheng C L, Ding Q B, Ding C M, et al. Screen of Bacillus subtilis mutants producing cytidine. Biotechnology, 2007, 17(5): 57-59.

[9] 黄艳辉, 魏志强, 徐庆阳, 等. 枯草芽孢杆菌产胞苷的初步研究. 生物技术通讯, 2007, 18(2): 255-257. Huang Y H, Wei Z Q, Xu Q Y, et al. Study on the breeding of cytidine -producing strain in Bacillus subtilis. Letters in Biotechnilogy, 2007, 18(2): 255-257.

[10] 魏志强, 徐庆阳, 刘淑云. 枯草芽孢杆菌生产胞苷的途径分析. 现代食品科技, 2008, 24(6): 544-547. Wei Z Q, Xu Q Y, Liu S Y. Metabolic pathway of cytidine synthesis in Bacillus Subtillis. Modern Food Science and Technology, 2008, 24(6):544-547.

[11] 张春艳, 丁庆豹, 许彦梅, 等. 胞苷生产菌的选育及发酵. 中国热带医学, 2009, 9(2): 241-243. Zhang C Y, Ding Q B, Xu Y M, et al. Screening and fermentation of cytidine-producing Bacillus subtilis mutants. China Tropical Medicine, 2009, 40(5): 455-459.

[12] 李登奎, 徐晓莉, 黄雷鸣, 等. 利用抗CTP合成酶反馈抑制筛选胞苷高产突变株. 中国药科大学学报,2009, 40(5): 455-459. Li D K, Xu X L, Huang L M, et al. Screening of cytidine-producing mutants based on feedback-inhibition resistance of CTP synthetase. Journal of China Pharmaceutical University, 2009, 40(5): 455-459.

[13] 苏静, 黄静, 谢希贤, 等. 枯草芽孢杆菌cdd基因敲除及对胞苷发酵的影响. 生物技术通讯, 2010, 21(1): 39-42. Su J, Huang J, Xie X X, et al. Knockout of the cdd gene in Bacillus subtilis and its influence on cytidine fermentation. Letters in Biotechnology, 2010, 21(1): 39-42.

[14] 苏静, 邓培生, 谢希贤, 等. 基于cdd基因敲除和嘧啶操纵子转移的胞苷产生菌的研究. 天津科技大学学报, 2010, 25(5): 1-5. Su J, Deng PS, Xie X X, et al. Study on cytidine producing strain based on cdd gene knockout and pyrimidine operon transfer. Journal of Tianjin University of Science & Technology, 2010, 25(5): 1-5.

[15] 方海田, 周运佼, 谢希贤, 等. 大肠杆菌ATCase抗反馈抑制突变体的构建及其对胞苷积累的影响. 天津科技大学学报, 2012, 27(4): 13-16. Fang H T, Zhou Y J, Xie X X, et al. Construction of ATCase mutants with feedback inhibition resistance and their effect on the cytidine production in E. coli. Journal of Tianjin University of Science & Technology, 2012, 27(4): 13-16.

[16] 方海田, 周运佼, 谢希贤, 等. 大肠杆菌cdd和 thrA基因的敲除及其对胞苷积累量的影响. 现代食品科技, 2012, 28(10):1306-1310. Fang H T, Zhou Y J, Xie X X, et al. Effect of gene knockout of cdd and thrA on cytidine production in E. coli. Modern Food Science and Technology, 2012, 28(10): 1306-1310.

[17] 吴晓娇, 孙家凯, 霍文婷, 等. 过表达carAB和pyrBI对大肠杆菌发酵胞苷的影响. 中国生物工程杂志,2012, 32(2): 39-44. Wu X J, Sun J K, Huo W T, et al. Effects of carAB and pyrBI overpression on cytidine fermentation in Escherichia coli. China Biotechnology, 2012, 32(2): 39-44.

[18] Satoru Asahi, Yutaka Tsunemi, Muneharu Doi. Improvement of cytidine producing mutant of Bacillus subtilis introducing a Mutation by homologous recombination. Biosci Biotech Biochem, 1995, 59(11): 2123-2126.

[19] Satoru Asahi, Yutaka Tsunemi. Cytidine production by mutants of Bacillus subtilis. Biosci Biotech Biochem,1996, 60(2): 353-354.

[20] Fang Haitian, Xie Xixian, Xu Qingyang, et al. Enhancement of cytidine production by coexpression of gnd, zwf and prs genes in recombinant Escherichia coli CYT 15. Biotechnologgy Letters, 2013, 35(2): 245-251.

[21] Fang Haitian, Zhang Chenglin, Xie Xixian, et al. Enhanced cytidine production by a recombinant Escherichia coli strain using genetic manipulation strategies. Annals of Microbiology, 2014, 64(3): 1203-1210.

[22] Charles L, Turnbough J, Robert L. Switzer.Regulation of pyrimidine biosynthetic gene expression in bacteria: Repression without repressors. Microbiology and Molecular Biology Reviews, 2008, 72(2): 266-300.

[23] Seul Keyung-Jo, Hyun-Soo Cho. Characterization of a PyrR-deficient mutant of Bacillus subtilis by a proteomic approach. Microbiol Biotechnol, 2011, 39(1): 9-19.

[24] Zhang H, Robert L S. Transcriptional pausing in the Bacillus subtilis pyr operon in vitro:A role in transcriptional attenuation. Journal of Bacteriology, 2003, 185, 4764-4771.

[25] Christopher J Fields, Robert L Switzer. Regulation of pyr gene expression in Mycobacterium smegmatis by PyrR-dependent translational repression. Journal of Bacteriology, 2007,189(17): 6236–6245.

[26] Fang Haitian, Xie Xixian, Xu Qingyang, et al. Enhancement of cytidine production by coexpression of gnd, zwf and prs genes in recombinant Escherichia coli CYT15. Biotechnol Lett, 2013, 35: 245–251.

[27] Azza Ramadan, Zlatina Naydenova, Katarina Stevanovic, et al. The adenosine transporter, ENT1, in cardiomyocytes is sensitive to inhibition by ethanol in a kinase-dependent manner: implications for ethanol-dependent cardioprotection and nucleoside analog drug cytotoxicity. Purinergic Signalling, 2014, 10(2): 305-312.

[28] 魏娜, 李柏林, 欧杰. 细胞膜通透性调节在发酵代谢中的重要性. 食品科技, 2006, 9: 14-17. Wei N, Li B L, Ou J. Role of cell membrane permeability controlon fermentation metabolic. Food Science and Technology, 2006, 9: 14-17.

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