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Applied Microbiology and Biotechnology

, Volume 101, Issue 4, pp 1351–1357 | Cite as

A genetic method to enhance the accumulation of S-adenosylmethionine in yeast

  • Muneyoshi Kanai
  • Masaki Mizunuma
  • Tsutomu Fujii
  • Haruyuki Iefuji
Mini-Review

Abstract

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.

Keywords

S-Adenosylmethionine Yeast Saccharomyces cerevisiae Pichia pastoris Sake yeast Methionine synthesis pathway 

Notes

Acknowledgements

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.

Ethical approval

This article does not contain any studies with human participants or animals performed by any of the authors.

References

  1. Ano A, Suehiro D, Cha-Aim K, Aritomi K, Phonimdaeng P, Nontaso N, Hoshida H, Mizunuma M, Miyakawa T, Akada R (2009) Combinatorial gene overexpression and recessive mutant gene introduction in sake yeast. Biosci Biotechnol Biochem 73:633–640. doi: 10.1271/bbb.80708 CrossRefPubMedGoogle Scholar
  2. Bell KM, Plon L, Bunney WE Jr, Potkin SG (1988) S-adenosylmethionine treatment of depression: a controlled clinical trial. Am J Psychiatry 145:1110–1114. doi: 10.1176/ajp.145.9.1110 CrossRefPubMedGoogle Scholar
  3. 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
  4. Breunig JS, Hackett SR, Rabinowitz JD, Kruglyak L (2014) Genetic basis of metabolome variation in yeast. PLoS Genet 10:e1004142. doi: 10.1371/journal.pgen.1004142 CrossRefPubMedPubMedCentralGoogle Scholar
  5. 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
  6. 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
  7. Christopher SA, Melnyk S, James SJ, Kruger WD (2002) S-adenosylhomocysteine, but not homocysteine, is toxic to yeast lacking cystathionine beta-synthase. Mol Genet Metab 75:335–343. doi: 10.1016/S1096-7192(02)00003-3 CrossRefPubMedGoogle Scholar
  8. Den Heijer M, Lewington S, Clarke R (2005) Homocysteine, MTHFR and risk of venous thrombosis: a meta-analysis of published epidemiological studies. J Thromb Haemost 3:292–299. doi: 10.1111/j.1538-7836.2005.01141.x CrossRefPubMedGoogle Scholar
  9. Fava M, Giannelli A, Rapisarda V, Patralia A, Guaraldi GP (1995) Rapidity of onset of the antidepressant effect of parenteral S-adenosyl-l-methionine. Psychiatry Res 56:295–297. doi: 10.1016/0165-1781(95)02656-H CrossRefPubMedGoogle Scholar
  10. Guruswamy S, Swamy MV, Choi CI, Steele VE, Rao CV (2008) S-adenosyl l-methionine inhibits azoxymethane-induced colonic aberrant crypt foci in F344 rats and suppresses human colon cancer Caco-2 cell growth in 3D culture. Int J Cancer 122:25–30. doi: 10.1002/ijc.23031 CrossRefPubMedGoogle Scholar
  11. Hayakawa K, Kajihata S, Matsuda F, Shimizu H (2015) 13C-metabolic flux analysis in S-adenosyl-l-methionine production by Saccharomyces cerevisiae. J Biosci Bioeng 120:532–538. doi: 10.1016/j.jbiosc.2015.03.010 CrossRefPubMedGoogle Scholar
  12. 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
  13. Huang L, Wei PL, Zang R, Xu ZN, Cen PL (2010) High-throughput screening of high-yield colonies of Rhizopus oryzae for enhanced production of fumaric acid. Ann Microbiol 60:287–292. doi: 10.1007/s13213-010-0039-y CrossRefGoogle Scholar
  14. Hvorup RN, Winnen B, Chang AB, Jiang Y, Zhou XF, Saier MH Jr (2003) The multidrug/oligosaccharidyl-lipid/polysaccharide (MOP) exporter superfamily. Eur J Biochem 270:799–813. doi: 10.1046/j.1432-1033.2003.03418.x CrossRefPubMedGoogle Scholar
  15. Inoue T, Iefuji H, Fujii T, Soga H, Satoh K (2000) Cloning and characterization of a gene complementing the mutation of an ethanol-sensitive mutant of sake yeast. Biosci Biotechnol Biochem 64:229–236. doi: 10.1271/bbb.64.229 CrossRefPubMedGoogle Scholar
  16. Izu H, Shobayashi M, Manabe Y, Goto K, Iefuji H (2006) S-Adenosylmethionine (SAM)-accumulating sake yeast suppresses acute alcohol-induced liver injury in mice. Biosci Biotechnol Biochem 70:2982–2989. doi: 10.1271/bbb.60377 CrossRefPubMedGoogle Scholar
  17. Jänne J, Alhonen L, Pietilä M, Keinänen TA (2004) Genetic approaches to the cellular functions of polyamines in mammals. Eur J Biochem 271:877–894. doi: 10.1111/j.1432-1033.2004.04009.x CrossRefPubMedGoogle Scholar
  18. 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
  19. 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
  20. Lee SW, Park BS, Choi ES, Oh MK (2010) Overexpression of ethionine resistance gene for maximized production of S-adenosylmethionine in Saccharomyces cerevisiae sake kyokai No. 6. Korean J Chem Eng 27:587–589. doi: 10.1007/s11814-010-0100-3 CrossRefGoogle Scholar
  21. Lieber CS (2002) S-adenosyl-l-methionine: its role in the treatment of liver disorders. Am J Clin Nutr 76:1183S–1187SPubMedGoogle Scholar
  22. Martínez-Chantar ML, García-Trevijano ER, Latasa MU, Pérez-Mato I, Sánchez del Pino MM, Corrales FJ, Avila MA, Mato JM (2002) Importance of a deficiency in S-adenosyl-l-methionine synthesis in the pathogenesis of liver injury. Am J Clin Nutr 76:1177S–1182SPubMedGoogle Scholar
  23. McCully KS (1969) Vascular pathology of homocysteinemia: implications for the pathogenesis of arteriosclerosis. Am J Pathol 56:111–128PubMedPubMedCentralGoogle Scholar
  24. Mischoulon D, Fava M (2002) Role of S-adenosyl-l-methionine in the treatment of depression: a review of the evidence. Am J Clin Nutr 76:1158S–1161SPubMedGoogle Scholar
  25. Mizunuma M, Miyamura K, Hirata D, Yokoyama H, Miyakawa T (2004) Involvement of S-adenosylmethionine in G1 cell-cycle regulation in Saccharomyces cerevisiae. Proc Natl Acad Sci U S A 101:6086–6091. doi: 10.1073/pnas.0308314101 CrossRefPubMedPubMedCentralGoogle Scholar
  26. 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
  27. Morrison LD, Smith DD, Kish SJ (1996) Brain S-adenosylmethionine levels are severely decreased in Alzheimer’s disease. J Neurochem 67:1328–1331. doi: 10.1046/j.1471-4159.1996.67031328.x CrossRefPubMedGoogle Scholar
  28. Obata F, Miura M (2015) Enhancing S-adenosyl-methionine catabolism extends Drosophila lifespan. Nat Commun 6:8332. doi: 10.1038/ncomms9332 CrossRefPubMedPubMedCentralGoogle Scholar
  29. Ogawa T, Tsubakiyama R, Kanai M, Koyama T, Fujii T, Iefuji H, Soga T, Kume K, Miyakawa T, Hirata D, Mizunuma M (2016) Stimulating S-adenosyl-l-methionine synthesis extends lifespan via activation of AMPK. Proc Natl Acad Sci 113:11913–11918. doi: 10.1073/pnas.1604047113 CrossRefPubMedGoogle Scholar
  30. Purohit V, Russo D (2002) Role of S-adenosyl-l-methionine in the treatment of alcoholic liver disease: introduction and summary of the symposium. Alcohol 27:151–154. doi: 10.1016/S0741-8329(02)00232-X CrossRefPubMedGoogle Scholar
  31. Schlenk F, Zydek CR (1967) The radiopurity of S-adenosylmethionine and S-adenosylethionine preparations. J Labelled Compounds 3:137–143. doi: 10.1002/jlcr.2590030209 CrossRefGoogle Scholar
  32. 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
  33. Shiomi N, Fukuda H, Murata K, Kimura A (1995) Improvement of S-adenosylmethionine production by integration of the ethionine-resistance gene into chromosomes of the yeast Saccharomyces cerevisiae. Appl Microbiol Biotechnol 42:730–733. doi: 10.1007/BF00171953 CrossRefPubMedGoogle Scholar
  34. Shiozaki S, Shimizu S, Yamada H (1984) Unusual intracellular accumulation of S-adenosyl-l-methionine by microorganisms. Agric Biol Chem 48:2293–2300. doi: 10.1271/bbb1961.48.2293 Google Scholar
  35. Shippy RA, Mendez D, Jones K, Cergnul I, Karpiak SE (2004) S-adenosylmethionine (SAM-e) for the treatment of depression in people living with HIV/AIDS. BMC Psychiatry 4:1–6. doi: 10.1186/1471-244X-4-38 CrossRefGoogle Scholar
  36. Shobayashi M, Mukai N, Iwashita K, Hiraga Y, Iefuji H (2006) A new method for isolation of S-adenosylmethionine (SAM)-accumulating yeast. Appl Microbiol Biotechnol 69:704–710. doi: 10.1007/s00253-005-0009-7 CrossRefPubMedGoogle Scholar
  37. Sridhar M, KiranSree N, Venkateswa RL (2002) Effect of UV radiation on thermotolerance, ethanol tolerance and osmotolerance of Saccharomyces cerevisiae VS1 and VS3 strains. Bioresour Technol 83:199–202. doi: 10.1016/S0960-8524(01)00221-8 CrossRefPubMedGoogle Scholar
  38. Thomas D, Rothstein R, Rosenberg N, Surdin-Kerjan Y (1988) SAM2 encodes the second methionine S-adenosyl transferase in Saccharomyces cerevisiae. Mol Cell Biol 8:5132–5139. doi: 10.1128/MCB.8.12.5132 CrossRefPubMedPubMedCentralGoogle Scholar
  39. 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

Copyright information

© Springer-Verlag Berlin Heidelberg 2017

Authors and Affiliations

  1. 1.National Research Institute of BrewingHiroshimaJapan
  2. 2.Hiroshima Research Center for Healthy Aging, Graduate School of Advanced Sciences of MatterHiroshima UniversityHiroshimaJapan
  3. 3.Graduate School of Biosphere ScienceHiroshima UniversityHiroshimaJapan
  4. 4.Present Address: Faculty of AgricultureEhime UniversityMatsuyamaJapan

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