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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  2018, Vol. 38 Issue (2): 102-108    DOI: 10.13523/j.cb.20180215
综述     
微生物发酵法生产环磷酸腺苷研究进展 *
程丽娜1,2,陆海燕1,2,曲淑玲3,张轶群3,丁娟娟1,2,邹少兰1,2*()
1 天津大学化工学院 天津 300350
2 系统生物工程教育部重点实验室 天津 300350
3 中国石油大港油田团泊洼开发公司 天津 301607
Production of Cyclic Adenosine Monophosphate (cAMP) by Microbial Fermentation——A Review
Li-na CHENG1,2,Hai-yan LU1,2,Shu-ling QU3,Yi-qun ZHANG3,Juan-juan DING1,2,Shao-lan ZOU1,2*()
1 School of Chemical Engineering and Technology,Tianjin University,Tianjin 300350,China
2 Key Laboratory of Systems Bioengineering,Ministry of Education,Tianjin 300350,China
3 PetroChina Dagang Oilfield In Tuanbowa Development Company, Tianjin 301607, China
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摘要：

环磷酸腺苷(3’,5’-cyclic adenosine monophosphate,cAMP)是普遍存在于生物机体内并起着十分重要作用的生理活性物质,称为第二信使。cAMP于1957年被首次发现报道,随后因为它在生命活动中的特殊地位和作用而被大量研究,外源性cAMP早在上世纪70年代就已开发成人类临床药物,在动物生产领域也有极大的潜在应用价值。目前已知临床用cAMP原料药全部由化学法合成。而微生物发酵法生产菌种则以节杆菌、枯草芽孢杆菌和酵母为代表;运用代谢调控机理和技术,用节杆菌发酵生产cAMP的产量据报道已达≥7.23 g/L,用枯草芽孢杆菌也已达到6~7 g/L,而酵母作为典型的模式生物,虽然cAMP-PKA信号转导途径基础研究历史悠久,但发酵生产cAMP则近几年才有报道。目前,除了进一步改造菌株、优化发酵技术提高产量和解决分离提纯问题外,充分发挥微生物发酵法的潜力和优势、弥补化学法合成的不足,是赢得其产业化契机的关键。
关键词： 环磷酸腺苷;  化学合成;  微生物发酵;  代谢工程    
Abstract:

3’,5’-cyclic adenosine monophosphate (cAMP), an important and active compound due to its participation in various physiological actions, acts as a key second messenger. It was first reported in 1957. Since then a lot of research had been carried on for its numerous functions. Exogenous cAMP was developed as pharmaceuticals early in 1970s and it has also been proved to have a great potential in animal husbandry. Now the known cAMP API (Active Pharmaceutical Ingredient) was all produced by chemical synthesis. On the other hand, the species used by microbial cAMP fermentation research includes Arthrobacter, Bacillus subtilis and yeast. As a result of utilizing metabolic regulation mechanism and technology, the extracellular cAMP level could reach ≥7.23 g/L for Arthrobacter and 6~7 g/L for Bacillus subtilis. High levels of extracellular cAMP production by Saccharomyces cerevisiae were reported in recent years. In order to make full use of microbial fermentation and realize its industrial production, it needs to further improve the performance of fermenting microorganisms and the fermentation technology, solve the scale-up problem and make the process more economic.
Key words: cAMP    Chemical synthesis    Microbial fermentation    Metabolic engineering
收稿日期: 2017-09-28 出版日期: 2018-03-21
ZTFLH:  Q819  
基金资助: * 国家自然科学基金资助项目(31470208)
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引用本文:

程丽娜,陆海燕,曲淑玲,张轶群,丁娟娟,邹少兰. 微生物发酵法生产环磷酸腺苷研究进展 *[J]. 中国生物工程杂志, 2018, 38(2): 102-108.

Li-na CHENG,Hai-yan LU,Shu-ling QU,Yi-qun ZHANG,Juan-juan DING,Shao-lan ZOU. Production of Cyclic Adenosine Monophosphate (cAMP) by Microbial Fermentation——A Review. China Biotechnology, 2018, 38(2): 102-108.

链接本文:

https://manu60.magtech.com.cn/biotech/CN/10.13523/j.cb.20180215    或    https://manu60.magtech.com.cn/biotech/CN/Y2018/V38/I2/102

图1  酵母嘌呤代谢及cAMP合成途径
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