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Genetic Modification and Bioprocess Optimization for S-Adenosyl-L-methionine Biosynthesis

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Reprogramming Microbial Metabolic Pathways

Part of the book series: Subcellular Biochemistry ((SCBI,volume 64))

Abstract

S-Adenosyl-L-methionine is an important bioactive sulfur-containing amino acid. Large scale preparation of the amino acid is of great significance. S-Adenosyl-L-methionine can be synthesized from L-methionine and adenosine triphosphate in a reaction catalyzed by methionine adenosyltransferase. In order to enhance S-adenosyl-L-methionine biosynthesis by industrial microbial strains, various strategies have been employed to optimize the process. Genetic manipulation has largely focused on enhancement of expression and activity of methionine adenosyltransferase. This has included its overexpression in Pichia pastoris, Saccharomyces cerevisiae and Escherichia coli, molecular evolution, and fine-tuning of expression by promoter engineering. Furthermore, knocking in of Vitreoscilla hemoglobin and knocking out of cystathionine-β-synthase have also been effective strategies. Besides genetic modification, novel bioprocess strategies have also been conducted to improve S-adenosyl-L-methionine synthesis and inhibit its conversion. This has involved the optimization of feeding modes of methanol, glycerol and L-methionine substrates. Taken together considerable improvements have been achieved in S-adenosyl-L-methionine accumulation at both flask and fermenter scales. This review provides a contemporary account of these developments and identifies potential methods for further improvements in the efficiency of S-adenosyl-L-methionine biosynthesis.

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Abbreviations

ATP:

Adenosine triphosphate

CBS:

Cystathionine-β-synthase

C-source:

Carbon source

L-Met:

L-methionine

MAT:

Methionine adenosyltransferase

PAOX :

Promoter of alcohol oxidase 1 gene

PGAP :

Promoter of glyceraldehyde-3-phosphate dehydrogenase gene

SAH:

S-adenosyl-L-homocysteine

SAM:

S-adenosyl-L-methionine

VHb:

Vitreoscilla hemoglobin

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Acknowledgements

Funding was provided by grants from National key Basic Research Program of China (2012CB725202), the Public Topic of Key Laboratory of Industrial Biotechnology, Ministry of Education (KLIB-KF201003) and State Key Laboratory of Food Science and Technology, Jiangnan University (SKLF-TS-201124).

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Authors and Affiliations

  1. State Key Laboratory of Food Science and Technology, Jiangnan University, 1800 Lihu Avenue, Wuxi, 214122, China

    Xiaoqing Hu & Xiaoyuan Wang

  2. Department of Biochemistry, King’s College London, 150 Stamford Street, London, SE1 9NH, UK

    Peter J. Quinn

  3. Key Laboratory of Industrial Biotechnology, Ministry of Education, School of Biotechnology, Jiangnan University, 1800 Lihu Avenue, Wuxi, 214122, China

    Zhou Wang & Guoqiang Han

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  1. Xiaoqing Hu
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  3. Zhou Wang
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Correspondence to Xiaoyuan Wang .

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  1. , State Key Laboratory, Jiangnan University, Lihu Avenue 1800, Wuxi, 214122, Jiangsu, China, People's Republic

    Xiaoyuan Wang

  2. School of Biotechnology, Jiangnan University, Lihu Avenue 1800, Wuxi, 214122, China, People's Republic

    Jian Chen

  3. , Div. of Life Sciences, King's College London, Stamford Street 150, London, SE1 9NH, United Kingdom

    Peter Quinn

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Hu, X., Quinn, P.J., Wang, Z., Han, G., Wang, X. (2012). Genetic Modification and Bioprocess Optimization for S-Adenosyl-L-methionine Biosynthesis. In: Wang, X., Chen, J., Quinn, P. (eds) Reprogramming Microbial Metabolic Pathways. Subcellular Biochemistry, vol 64. Springer, Dordrecht. https://doi.org/10.1007/978-94-007-5055-5_16

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