A genetic method to enhance the accumulation of S-adenosylmethionine in yeast
- 667 Downloads
S-Adenosylmethionine (SAM) is a key component of sulphur amino acid metabolism in living organisms and is synthesised from methionine and adenosine triphosphate by methionine adenosyltransferase. This molecule serves as the main biological methyl donor due to its active methylthio ether group. Notably, SAM has shown beneficial effects in clinical trials for the treatment of alcoholic liver disease, depression and joint pain. Due to the high potential value of SAM, current research efforts are attempting to develop a more rapid, cost-effective and higher yielding SAM production method than the conventional production system. In this mini-review, we describe the previously reported yeast gene that contributes to SAM accumulation by overexpression, mutation or deletion and summarise the genetic approach for the production of SAM in large industrial quantities.
KeywordsS-Adenosylmethionine Yeast Saccharomyces cerevisiae Pichia pastoris Sake yeast Methionine synthesis pathway
We thank Dr. Dai Hirata (Hiroshima University and Asahi-Shuzo Sake Brewing Co., Ltd.), Dr. Kazunori Kume, Takafumi Ogawa (Hiroshima University), Dr. Osamu Yamada, Akihiro Mizuno, Dr. Kazuo Masaki, Dr. Hiroko Ikeda, Yasumichi Takaoka, Mitsunori Masuda, Yoshie Yoshida, Yasuko Kita, Tomoko Kawata (NRIB), Dr. Daisuke Watanabe (Nara Institute of Science and Technology) and Dr. Hitoshi Shimoi (Iwate University) for their constant guidance, support and helpful discussions.
Compliance with ethical standards
Conflict of interest
The authors declare that they have no competing interests.
This article does not contain any studies with human participants or animals performed by any of the authors.
- Bradley JD, Flusser D, Katz BP, Schumacher HR Jr, Brandt KD, Chambers MA, Zonay LJ (1994) A randomized, double blind, placebo controlled trial of intravenous loading with S-adenosylmethionine (SAM) followed by oral SAM therapy in patients with knee osteoarthritis. J Rheumatol 21:905–911PubMedGoogle Scholar
- Cao X, Yang M, Xia Y, Dou J, Chen K, Wang H, Xi T, Zhou C (2012) Strain improvement for enhanced production of S-adenosyl-l-methionine in Saccharomyces cerevisiae based on ethionine-resistance and SAM synthetase activity. Ann Microbiol 62:1395–1402. doi: 10.1007/s13213-011-0389-0 CrossRefGoogle Scholar
- Chen H, Wang Z, Wang Z, Dou J, Zhou C (2016) Improving methionine and ATP availability by MET6 and SAM2 co-expression combined with sodium citrate feeding enhanced SAM accumulation in Saccharomyces cerevisiae. World J Microbiol Biotechnol 32:56. doi: 10.1007/s11274-016-2010-y CrossRefPubMedGoogle Scholar
- He J, Deng J, Zheng Y, Gu J (2006) A synergistic effect on the production of S-adenosyl-l-methionine in Pichia pastoris by knocking in of S-adenosyl-l-methionine synthase and knocking out of cystathionine-beta synthase. J Biotechnol 126:519–527. doi: 10.1016/j.jbiotec.2006.05.009 CrossRefPubMedGoogle Scholar
- Kanai M, Masuda M, Takaoka Y, Ikeda H, Masaki K, Fujii T, Iefuji H (2013) Adenosine kinase-deficient mutant of Saccharomyces cerevisiae accumulates S-adenosylmethionine because of an enhanced methionine biosynthesis pathway. Appl Microbiol Biotechnol 97:1183–1190. doi: 10.1007/s00253-012-4261-3 CrossRefPubMedGoogle Scholar
- Kanai M, Kawata T, Yoshida Y, Kita Y, Ogawa T, Mizunuma M, Watanabe D, Shimoi H, Mizuno A, Yamada O, Fujii T, Iefuji H (2017) Sake yeast YHR032W/ERC1 haplotype contributes to high S-adenosylmethionine accumulation in sake yeast strains. J Biosci Bioeng 123:8–14. doi: 10.1016/j.jbiosc.2016.07.007 CrossRefPubMedGoogle Scholar
- Monoi N, Matsuno A, Nagamori Y, Kimura E, Nakamura Y, Oka K, Sano T, Midorikawa T, Sugafuji T, Murakoshi M, Uchiyama A, Sugiyama K, Nishino H, Urade Y (2016) Japanese sake yeast supplementation improves the quality of sleep: a double-blind randomised controlled clinical trial. J Sleep Res 25:116–123. doi: 10.1111/jsr.12336 CrossRefPubMedGoogle Scholar
- Schosserer M, Minois N, Angerer TB, Amring M, Dellago H, Harreither E, Calle-Perez A, Pircher A, Gerstl MP, Pfeifenberger S, Brandl C, Sonntagbauer M, Kriegner A, Linder A, Weinhäusel A, Mohr T, Steiger M, Mattanovich D, Rinnerthaler M, Karl T, Sharma S, Entian KD, Kos M, Breitenbach M, Wilson IB, Polacek N, Grillari-Voglauer R, Breitenbach-Koller L, Grillari J (2015) Methylation of ribosomal RNA by NSUN5 is a conserved mechanism modulating organismal lifespan. Nat Commun 6:6158. doi: 10.1038/ncomms7158 CrossRefPubMedPubMedCentralGoogle Scholar
- Zhao W, Shi F, Hang B, Huang L, Cai J, Xu Z (2016) 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. doi: 10.1007/s12010-015-1943-1 CrossRefPubMedGoogle Scholar