S-adenosyl-L-methionine Production by Microorganism

Abstract

Abstract: S-adenosyl-L-methionine（SAM）is a type of active amino acid having broad market prospects，and there have been manyreports on SAM production catalyzed by microorganisms. This paper integrated advances in genetic modification and fermentation optimizationof SAM-producing strain. From the points of elevating expression and activity of SAM synthetase，optimizing feeding mode of glycerol andmethanol，improving the generation of ATP and supplement policy of L-methionine，and blocking downstream metabolic pathway，themultiple strategies of enhancing SAM synthesis and accumulation and their mechanisms had been reviewed. Furthermore，on the basis of theauthors’ research practice，some new prospects on SAM biosynthesis by microbes were discussed.

Hu Xiaoqing, Guo Wen, Han Guoqiang . S-adenosyl-L-methionine Production by Microorganism[J]. Biotechnology Bulletin, 2012, 0(12): 33-39.

References

[1] Matos JR, Raushel FM, Wong CH. S-adenosylmethionine: studieson chemical and enzymatic synthesis. Biotechnol Appl Biochem,1987, 9: 39-52.
[2] 公剑, 王旻, 韦和平. S-腺苷甲硫氨酸合成酶及其在S-腺苷甲硫氨酸合成中的应用. 药物生物技术, 2001, 8: 108-111.
[3] Park J, Tai J, Roessner AC, et al. Enzymatic synthesis of S-adenosyl-L-methionine on the preparative scale. Bioorg Med Chem, 1996, 4:2179-2185.
[4] Shiozaki S, Shimizu S, Yamada H. Unusual intracellular accumulationof S-adenosyl-L-methionine microorganism. Agric Biol Chem,1984, 48: 2293-2300.
[5] Takusagawa F, Kamitori S, Misaki S, et al. Crystal structure ofS-adenosylmethionine synthetase. J Biol Chem, 1996, 271: 136-147.
[6] Markham GD, DeParasis J, Gatmaitan J. The sequence of metK, thestructural gene for S-adenosylmethionine synthetase in Escherichiacoli. J Biol Chem, 1984, 259: 14505-14507.
[7] Satishchandran C, Taylor JC, Markham GD. Isozymes of S-adenosylmethioninesynthetase are encoded by tandemly duplicated genes inEscherichia coli. Mol Microbiol, 1993, 9: 835-846.
[8] Janne J, Schenone A, Williams-Ashman HG. Separation of twoproteins required for synthesis of spermidine from S-adenosyl-Lmethionineand putrescine in rat prostate. Biochem Biophys ResCommun, 1971, 42: 758-764.
[9] 李海军, 朱希强, 刘彩霞, 等. 酿酒酵母发酵生产S-腺苷甲硫氨酸工艺的优化. 食品与药品, 2008, 10: 13-18.
[10] 叶盛. S-腺苷甲硫氨酸高产菌株的筛选、诱变选育及其培养条件的优化[D] . 成都：四川师范大学, 2007.
[11] Mincheva KP, Balutsov VM. Isolation of S-adenosyl-L-methioninefrom an enriched Kluyveromyces lactis mutant, grown in wheymedia. Prikl Biokhim Mikrobiol, 2002, 38: 389-392.
[12] Shiomi N, Fukuda H, Murata K, et al. Improvement of S-adenosylmethionineproduction by integration of the ethionine-resistancegene into chromosomes of the yeast Saccharomyces cerevisiae. ApplMicrobiol Biotechnol, 1995, 42: 730-733.
[13] Li DY, Yu J, Tian L, et al. Production of SAM by recombinant Pichiapastoris. Sheng Wu Gong Cheng Xue Bao, 2002, 18: 295-299.
[14] 李东阳, 于健, 田露, 等. 利用重组Pichina pastoris 生产腺苷甲硫氨酸. 生物工程学报, 2003, 35: 127-132.
[15] Hu H, Qian J, Chu J, et al. DNA shuffling of methionine adenosyltransferasegene leads to improved S-adenosyl-L-methionineproduction in Pichia pastoris. J Biotechnol, 2009, 141: 97-103.
[16] Qin X, Qian J, Yao G, et al. GAP promoter library for fine-tuning ofgene expression in Pichia pastoris. Appl Environ Microbiol, 2011,77: 3600-3608.
[17] Hardison R. Hemoglobins from bacteria to man: evolution ofdifferent patterns of gene expression. J Exp Biol, 1998, 201: 1099-1117.
[18] Wakabayashi S, Matsubara H, Webster DA. Primary sequence ofa dimeric bacterial haemoglobin from Vitreoscilla. Nature, 1986,322: 481-483.
[19] Chen H, Chu J, Zhang S, et al. Intracellular expression ofVitreoscilla hemoglobin improves S-adenosylmethionine productionin a recombinant Pichia pastoris. Appl Microbiol Biotechnol, 2007,74: 1205-1212.
[20] 吕中原, 钱江潮, 储炬, 等. 同时利用AOX1 和GAP 启动子表达SAM 合成酶促进重组毕赤酵母中S-腺苷甲硫氨酸积累. 工业微生物杂志, 2008, 38: 24-32.
[21] He J, Deng J, Zheng Y, et al. A synergistic effect on the productionof S-adenosyl-L-methionine in Pichia pastoris by knockingin of S-adenosyl-L-methionine synthase and knocking out ofcystathionine-beta synthase. J Biotechnol, 2006, 126: 519-527.
[22] Markham GD, Hafner EW, Tabor CW, et al. S-Adenosylmethioninesynthetase from Escherichia coli. J Biol Chem, 1980, 255: 9082-9092.
[23] Zhang J, Wang X, Su E, et al. A new fermentation strategy forS-adenosylmethionine production in recombinant Pichia pastoris.Biochem Eng J, 2008, 41: 74-78.
[24] Hu X, Chu J, Zhang S, et al. A novel feeding strategy duringthe production phase for enhancing the enzymatic synthesis of S-adenosyl-l-methionine by methylotrophic Pichia pastoris. EnzymeMicrob Technol, 2007, 40: 669-674.
[25] Hu H, Qian J, Chu J, et al. Optimization of L: -methionine feedingstrategy for improving S-adenosyl-L: -methionine production bymethionine adenosyltransferase overexpressed Pichia pastoris. ApplMicrobiol Biotechnol, 2009, 83: 1105-1114.
[26] 刘沛溢, 董函竹, 潭天伟. 补加前体L- 蛋氨酸对亮密度发酵生产S- 腺苷-L- 蛋氨酸的影响. 生物工程学报, 2006, 22(2)：268-272.
[27] Wang J, Tan T. Pre-L-methionine feeding strategy for S-adenosyl-L-methionine fermentative production. Sheng Wu Gong Cheng XueBao, 2008, 24: 1824-1827.
[28] 朱闪, 储炬, 胡晓清, 等. 中心组合优化重组毕赤酵母生产S-腺苷甲硫氨酸用发酵培养基. 高技术通讯, 2006, 16: 181-186.
[29] Mincheva K, Kamburova V, Balutzov V. Production of S-adenosyl-L-methionine by a mutant strain of Kluyveromyces lactis. BiotechnolLett, 2002, 24: 985-988.
[30] Wang J, Han J, Li X, et al. Optimization of high-cell-densityfermentation process for S-adenosyl-L-methionine production.Sheng Wu Gong Cheng Xue Bao, 2009, 25: 533-536.
[31] Zhang JG, Wang XD, Zhang JN, et al. Oxygen vectors used forS-adenosylmethionine production in recombinant Pichia pastoriswith sorbitol as supplemental carbon source. J Biosci Bioeng, 2008,105: 335-340.
[32] Huang Y, Gou X, Hu H, et al. Enhanced S-adenosyl-l-methionineproduction in Saccharomyces cerevisiae by spaceflight culture,overexpressing methionine adenosyltransferase and optimizingcultivation. J Appl Microbiol, 2011, 112: 683-694.
[33] Hu XQ, Chu J, Zhang Z, et al. Effects of different glycerol feedingstrategies on S-adenosyl-L-methionine biosynthesis by PGAP-drivenPichia pastoris overexpressing methionine adenosyltransferase. JBiotechnol, 2008, 137: 44-9.
[34] Lee SW, Park BS, Choi ES, et al. Overexpression of ethionineresistance gene for maximized production of S-adenosylmethioninein Saccharomyces cerevisiae sake kyokai No. 6. Korean J Chem Eng,2010, 27: 587-9.