文献类型：期刊文献

英文题名：Progress in the research of S-adenosyl-L-methionine production

作者：Chu, Ju[1];Qian, Jiangchao[1];Zhuang, Yingping[1];Zhang, Siliang[1];Li, Yourong[1]

机构：[1]E China Univ Sci & Technol, State Key Lab Bioreactor Engn, Shanghai 200237, Peoples R China

年份：2013

卷号：97

期号：1

起止页码：41

外文期刊名：APPLIED MICROBIOLOGY AND BIOTECHNOLOGY

收录：;EI(收录号：20130415921605);WOS:【SCI-EXPANDED(收录号:WOS:000313065400004)】；

基金：This work was financially supported by grants from the Major State Basic Research Development Program of China (973 Program, 2012CB721006); the National Natural Science Foundation of China (20976065); the National Scientific and Technological Major Special Project (Significant Creation of New Drugs, no. 2011ZX09203-001-03); and the Chinese Doctoral Program of Higher Education of Specialized Research Fund (20110074110015).

语种：英文

外文关键词：S-adenosyl-L-methionine; L-Methionine; ATP; L-Methionine adenosyltransferase; Pichia pastoris

摘要：This minireview mainly aims at the study of S-adenosyl-l-methionine (SAM) production by microbial fermentation. A brief introduction of the biological role and application of SAM was presented. In general, SAM production can be improved by breeding of the producing strain through the conventional mutation or genetic engineering approach in the molecular or cellular scale, by optimization of culture conditions in the cellular scale or bioreactor engineering scale, or by multiscale approach. The productivity of SAM fermentation has been improved greatly through the efforts of many researchers using the methods previously mentioned. The SAM-producing strains used extensively are Pichia pastoris and Saccharomyces cerevisiae. The effect of SAM on antibiotic production was also exemplified. The skill and scheme beneficial to the improvement of SAM production involves the enhancement of SAM synthetase (methionine adenosyltransferase) activity and selection of engineered constitutive promoters with appropriate strength; seeking for and eliminating the rate-limiting factors in SAM synthesis, namely, knocking off the genes that transform SAM and l-methionine (L-Met) to cysteine; release the feedback inhibition of SAM to methylenetetrahydrofolate reductase; blocking the transsulfuration pathway by interfering the responsible enzymes; enhancing ATP level through pulsed feeding of glycerol; and optimizing the L-Met feeding strategy. Precise control of gene expression and quantitative assessment of physiological parameters in engineered P. pastoris were highlighted. Finally, a discussion of the prospect of SAM production was presented.