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Progress in the research of S-adenosyl-l-methionine production

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Abstract

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.

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Acknowledgments

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).

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  1. State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, 130 Meilong Road, P.O. Box 329, 200237, Shanghai, People’s Republic of China

    Ju Chu, Jiangchao Qian, Yingping Zhuang, Siliang Zhang & Yourong Li

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  1. Ju Chu
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  2. Jiangchao Qian
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Correspondence to Ju Chu.

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Chu, J., Qian, J., Zhuang, Y. et al. Progress in the research of S-adenosyl-l-methionine production. Appl Microbiol Biotechnol 97, 41–49 (2013). https://doi.org/10.1007/s00253-012-4536-8

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