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The Improvement of SAM Accumulation by Integrating the Endogenous Methionine Adenosyltransferase Gene SAM2 in Genome of the Industrial Saccharomyces cerevisiae Strain

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Abstract

S-Adenosyl-l-methionine (SAM) plays important roles in trans-methylation, trans-sulfuration, and polyamine synthesis in all living cells, and it is also an effective cure for liver disease, depressive syndromes, and osteoarthritis. The increased demands of SAM in pharmaceuticals industry have aroused lots of attempts to improve its production. In this study, a multiple-copy integrative plasmid pYMIKP-SAM2 was introduced into the chromosome of wild-type Saccharomyces cerevisiae strain ZJU001 to construct the recombined strain R1-ZJU001. Further studies showed that the recombinant yeast exhibited higher enzymatic activity of methionine adenosyltransferase and improved its SAM biosynthesis. With a three-phase fed-batch strategy in 15-liter bench-top fermentor, 8.81 g/L SAM was achieved after 52 h cultivation of R1-ZJU001, about 27.1 % increase over its parent strain ZJU001, whereas the SAM content was also improved from 64.6 mg/g DCW to 91.0 mg/g DCW. Our results shall provide insights into the metabolic engineering of SAM pathway in yeast for improved productivity of SAM and subsequent industrial applications.

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Acknowledgments

We thank Prof. Xiaoming Bao (State Key Laboratory of Microbial Technology, Shandong University, China) for the donation of Plasmid pYMIKP and her critical review of this manuscript. This work was financially supported by the National Natural Science Foundation of China (21176214, 21276226) and the National High Technology Research and Development Program of China (2012AA022105A, 2011AA02A114).

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Authors and Affiliations

  1. Key Laboratory of Biomass Chemical Engineering (Ministry of Education), College of Chemical and Biological Engineering, Zhejiang University, 38 Zheda Road, Hangzhou, 310027, China

    Weijun Zhao, Baojian Hang, Lei Huang, Jin Cai & Zhinan Xu

  2. Shandong Institute for Food and Drug Control, Jinan, 250101, China

    Feng Shi

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  1. Weijun Zhao
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  2. Feng Shi
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  3. Baojian Hang
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  4. Lei Huang
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  5. Jin Cai
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  6. Zhinan Xu
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Correspondence to Zhinan Xu.

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Zhao, W., Shi, F., Hang, B. et al. The Improvement of SAM Accumulation by Integrating the Endogenous Methionine Adenosyltransferase Gene SAM2 in Genome of the Industrial Saccharomyces cerevisiae Strain. Appl Biochem Biotechnol 178, 1263–1272 (2016). https://doi.org/10.1007/s12010-015-1943-1

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  • DOI: https://doi.org/10.1007/s12010-015-1943-1

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