Enhanced S-adenosyl-l-methionine production in Saccharomyces cerevisiae by spaceflight culture, overexpressing methionine adenosyltransferase and optimizing cultivation
Article first published online: 29 FEB 2012
© 2012 The Authors. Journal of Applied Microbiology © 2012 The Society for Applied Microbiology
Journal of Applied Microbiology
Volume 112, Issue 4, pages 683–694, April 2012
How to Cite
Huang, Y., Gou, X., Hu, H., Xu, Q., Lu, Y. and Cheng, J. (2012), Enhanced S-adenosyl-l-methionine production in Saccharomyces cerevisiae by spaceflight culture, overexpressing methionine adenosyltransferase and optimizing cultivation. Journal of Applied Microbiology, 112: 683–694. doi: 10.1111/j.1365-2672.2012.05251.x
- Issue published online: 13 MAR 2012
- Article first published online: 29 FEB 2012
- Accepted manuscript online: 7 FEB 2012 10:55AM EST
- 2011/0946: received 8 June 2011, revised 26 January 2012 and accepted 1 February 2012
- methionine adenosyltransferase;
- Saccharomyces cerevisiae;
Aims: S-adenosyl-l-methionine (SAM) is an important biochemical molecule with great potential in the pharmacological and chemotherapeutic fields. In this study, our aims were to enhance SAM production in Saccharomyces cerevisiae.
Methods and Results: Through spaceflight culture, a SAM-accumulating strain, S. cerevisiae H5M147, was isolated and found to produce 86·89% more SAM than its ground control strain H5. Amplified fragment length polymorphism (AFLP) analysis demonstrated that there were genetic variations between strain H5M147 and its ground control. Through recombinant DNA technology, the heterologous gene encoding methionine adenosyltransferase was integrated into the genome of strain H5M147. The recombinant strain H5MR83 was selected because its SAM production was increased by 42·98% when compared to strain H5M147. Furthermore, cultivation conditions were optimized using the one-factor-at-a-time and Taguchi methods. Under optimal conditions, strain H5MR83 yielded 7·76 g l−1 of SAM in shake flask, an increase of 536·07% when compared to the strain H5. Furthermore, 9·64 g l−1 of SAM was produced in fermenter cultivation.
Conclusions: A new SAM-accumulating strain, S. cerevisiae H5MR83, was obtained through spaceflight culture and genetic modification. Under optimal conditions, SAM production was increased to a relative high level in our study.
Significance and Impact of the Study: Through comprehensive application of multiple methods including spaceflight culture, genetic modification and optimizing cultivation, the yield of SAM could be increased by 6·4 times compared to that in the control strain H5. The obtained S. cerevisiae H5MR83 produced 7·76 g l−1 of SAM in the flask cultures, a significant improvement on previously reported results. The SAM production period with S. cerevisiae H5MR83 was 84 h, which is shorter than previously reported results. Saccharomyces cerevisiae H5MR83 has considerable potential for use in industrial applications.