Skip to main content
Log in

The metabolism and biotechnological application of betaine in microorganism

  • Mini-Review
  • Published:
Applied Microbiology and Biotechnology Aims and scope Submit manuscript

Abstract

Glycine betaine (betaine) is widely distributed in nature and can be found in many microorganisms, including bacteria, archaea, and fungi. Due to its particular functions, many microorganisms utilize betaine as a functional chemical and have evolved different metabolic pathways for the biosynthesis and catabolism of betaine. As in animals and plants, the principle role of betaine is to protect microbial cells against drought, osmotic stress, and temperature stress. In addition, the role of betaine in methyl group metabolism has been observed in a variety of microorganisms. Recent studies have shown that betaine supplementation can improve the performance of microbial strains used for the fermentation of lactate, ethanol, lysine, pyruvate, and vitamin B12, during which betaine can act as stress protectant or methyl donor for the biosynthesis of structurally complex compounds. In this review, we summarize the transport, synthesis, catabolism, and functions of betaine in microorganisms and discuss potential engineering strategies that employ betaine as a methyl donor for the biosynthesis of complex secondary metabolites such as a variety of vitamins, coenzymes, and antibiotics. In conclusion, the biocompatibility, C/N ratio, abundance, and comprehensive metabolic information of betaine collectively indicate that this molecule has great potential for broad applications in microbial biotechnology.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2

Similar content being viewed by others

References

  • Annamalai T, Venkitanarayanan K (2009) Role of proP and proU in betaine uptake by Yersinia enterocolitica under cold and osmotic stress conditions. Appl Environ Microbiol 75(6):1471–1477

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ashraf M, Foolad MR (2007) Roles of glycine betaine and proline in improving plant abiotic stress resistance. Environ Exp Bot 59(2):206–216

    Article  CAS  Google Scholar 

  • Barra L, Fontenelle C, Ermel G, Trautwetter A, Walker GC, Blanco C (2006) Interrelations between glycine betaine catabolism and methionine biosynthesis in Sinorhizobium meliloti strain 102F34. J Bacteriol 188(20):7195–7204

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Boncompagni E, Osteras M, Poggi MC, le Rudulier D (1999) Occurrence of choline and glycine betaine uptake and metabolism in the family Rhizobiaceae and their roles in osmoprotection. Appl Environ Microbiol 65(5):2072–2077

    CAS  PubMed  PubMed Central  Google Scholar 

  • Brown AD (1976) Microbial water stress. Bacteriol Rev 40(4):803–846

    CAS  PubMed  PubMed Central  Google Scholar 

  • Cairney J, Booth IR, Higgins CF (1985a) Osmoregulation of gene expression in Salmonella typhimurium: proU encodes an osmotically induced betaine transport system. J Bacteriol 164(3):1224–1232

    CAS  PubMed  PubMed Central  Google Scholar 

  • Cairney J, Booth IR, Higgins CF (1985b) Salmonella typhimurium proP gene encodes a transport system for the osmoprotectant betaine. J Bacteriol 164(3):1218–1223

    CAS  PubMed  PubMed Central  Google Scholar 

  • Chen SY, Lai MC, Lai SJ, Lee YC (2009) Characterization of osmolyte betaine synthesizing sarcosine dimethylglycine N-methyltransferase from Methanohalophilus portucalensis. Arch Microbiol 191(10):735–743

    Article  CAS  PubMed  Google Scholar 

  • Choquet G, Jehan N, Pissavin C, Blanco C, Jebbar M (2005) OusB, a broad-specificity ABC-type transporter from Erwinia chrysanthemi, mediates uptake of glycine betaine and choline with a high affinity. Appl Environ Microbiol 71(7):3389–3398

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Claesen J, Bibb M (2010) Genome mining and genetic analysis of cypemycin biosynthesis reveal an unusual class of posttranslationally modified peptides. Proc Natl Acad Sci 107(37):16297–16302

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Cluis CP, Burja AM, Martin VJ (2007) Current prospects for the production of coenzyme Q10 in microbes. Trends Biotechnol 25(11):514–521

    Article  CAS  PubMed  Google Scholar 

  • Craciun S, Balskus EP (2012) Microbial conversion of choline to trimethylamine requires a glycyl radical enzyme. Proc Natl Acad Sci 109(52):21307–21312

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Craig SA (2004) Betaine in human nutrition. Am J Clin Nutr 80(3):539–549

    CAS  PubMed  Google Scholar 

  • Culham DE, Lasby B, Marangoni AG, Milner JL, Steer BA, van Nues RW, Wood JM (1993) Isolation and sequencing of Escherichia coli gene prop reveals unusual structural features of the osmoregulatory proline betaine transporter, prop. J Mol Bio 229(1):268–276

    Article  CAS  Google Scholar 

  • Diamant S, Rosenthal D, Azem A, Eliahu N, Ben-Zvi AP, Goloubinoff P (2003) Dicarboxylic amino acids and glycine-betaine regulate chaperone-mediated protein-disaggregation under stress. Mol Microbiol 49(2):401–410

    Article  CAS  PubMed  Google Scholar 

  • Dickens ML, Ye J, Strohl WR (1995) Analysis of clustered genes encoding both early and late steps in daunomycin biosynthesis by Streptomyces sp. strain C5. J Bacteriol 177(3):536–543

    CAS  PubMed  PubMed Central  Google Scholar 

  • Ding W, Deng W, Tang M, Zhang Q, Tang G, Bi Y, Liu W (2010) Biosynthesis of 3-methoxy-5-methyl naphthoic acid and its incorporation into the antitumor antibiotic azinomycin B. Mol BioSyst 6(6):1071–1081

    Article  CAS  PubMed  Google Scholar 

  • Duan XG, Chen J, Wu J (2013) Optimization of pullulanase production in Escherichia coli by regulation of process conditions and supplement with natural osmolytes. Bioresour Technol 146:379–385

    Article  CAS  PubMed  Google Scholar 

  • Eklund M, Bauer E, Wamatu J, Mosenthin R (2005) Potential nutritional and physiological functions of betaine in livestock. Nutr Res Rev 18(1):31–48

    Article  CAS  PubMed  Google Scholar 

  • Feng J, Wu J, Gao J, Xia Z, Deng Z, He X (2014) Biosynthesis of the beta-methylarginine residue of peptidyl nucleoside arginomycin in Streptomyces arginensis NRRL 15941. Appl Environ Microbiol 80(16):5021–5027

    Article  PubMed  PubMed Central  Google Scholar 

  • Frossard SM, Khan AA, Warrick EC, Gately JM, Hanson AD, Oldham ML, Sanders DA, Csonka LN (2012) Identification of a third osmoprotectant transport system, the osmU system, in Salmonella enterica. J Bacteriol 194(15):3861–3871

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Galinski EA, Truper HG (1982) Betaine, a compatible solute in the extremely halophilic phototropic bacterium Ectothiorhodospira Halochloris. FEMS Microbiol Lett 13(4):357–360

    Article  CAS  Google Scholar 

  • Galinski EA, Truper HG (1994) Microbial behavior in salt-stressed ecosystems. FEMS Microbiol Rev 15(2–3):95–108

    Article  CAS  Google Scholar 

  • Glaasker E, Heuberger EH, Konings WN, Poolman B (1998) Mechanism of osmotic activation of the quaternary ammonium compound transporter (QacT) of Lactobacillus plantarum. J Bacteriol 180(21):5540–5546

    CAS  PubMed  PubMed Central  Google Scholar 

  • González JC, Peariso K, Penner-Hahn JE, Matthews RG (1996) Cobalamin-independent methionine synthase from Escherichia coli: a zinc metalloenzyme. Biochemistry 35(38):12228–12234

    Article  PubMed  Google Scholar 

  • Gouesbet G, Jebbar M, Talibart R, Bernard T, Blanco C (1994) Pipecolic acid is an osmoprotectant for Escherichia coli taken up by the general osmoporters prou and prop. Microbiol-Uk 140:2415–2422

    Article  CAS  Google Scholar 

  • Gouesbet G, Trautwetter A, Bonnassie S, Wu LF, Blanco C (1996) Characterization of the Erwinia chrysanthemi osmoprotectant transporter gene ousA. J Bacteriol 178(2):447–455

    CAS  PubMed  PubMed Central  Google Scholar 

  • Ikuta S, Imamura S, Misaki H, Horiuti Y (1977) Purification and characterization of choline-oxidase from Arthrobacter globiformis. J Biochem 82(6):1741–1749

    CAS  PubMed  Google Scholar 

  • Kacprzak MM, Lewandowska I, Matthews RG, Paszewski A (2003) Transcriptional regulation of methionine synthase by homocysteine and choline in Aspergillus nidulans. Biochem J 376(Pt 2):517–524

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kang SY, Lee JK, Choi O, Kim CY, Jang JH, Hwang BY, Hong YS (2014) Biosynthesis of methylated resveratrol analogs through the construction of an artificial biosynthetic pathway in E. coli. BMC Biotechnol 14:67

    Article  PubMed  PubMed Central  Google Scholar 

  • Kappes RM, Kempf B, Bremer E (1996) Three transport systems for the osmoprotectant glycine betaine operate in Bacillus subtilis: characterization of OpuD. J Bacteriol 178(17):5071–5079

    CAS  PubMed  PubMed Central  Google Scholar 

  • Kato N, Suzuki H, Okumura H, Takahashi S, Osada H (2013) A point mutation in ftmD blocks the fumitremorgin biosynthetic pathway in Aspergillus fumigatus strain Af293. Biosci Biotechnol Biochem 77(5):1061–1067

    Article  CAS  PubMed  Google Scholar 

  • Kempf B, Bremer E (1995) OpuA, an osmotically regulated binding protein-dependent transport system for the osmoprotectant glycine betaine in Bacillus subtilis. J Biol Chem 270(28):16701–16713

    Article  CAS  PubMed  Google Scholar 

  • Kempf B, Bremer E (1998) Uptake and synthesis of compatible solutes as microbial stress responses to high-osmolality environments. Arch Microbiol 170(5):319–330

    Article  CAS  PubMed  Google Scholar 

  • Lai MC, Yang DR, Chuang MJ (1999) Regulatory factors associated with synthesis of the osmolyte glycine betaine in the halophilic methanoarchaeon Methanohalophilus portucalensis. Appl Environ Microbiol 65(2):828–833

    CAS  PubMed  PubMed Central  Google Scholar 

  • Lai MC, Hong TY, Gunsalus RP (2000) Glycine betaine transport in the obligate halophilic archaeon Methanohalophilus portucalensis. J Bacteriol 182(17):5020–5024

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lambou K, Pennati A, Valsecchi I, Tada R, Sherman S, Sato H, Beau R, Gadda G, Latge JP (2013) Pathway of glycine betaine biosynthesis in Aspergillus fumigatus. Eukaryot Cell 12(6):853–863

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Landfald B, Strom AR (1986) Choline-glycine betaine pathway confers a high-level of osmotic tolerance in Escherichia coli. J Bacteriol 165(3):849–855

    CAS  PubMed  PubMed Central  Google Scholar 

  • Lee PT, Hsu AY, Ha HT, Clarke CF (1997) A C-methyltransferase involved in both ubiquinone and menaquinone biosynthesis: isolation and identification of the Escherichia coli ubiE gene. J Bacteriol 179(5):1748–1754

    CAS  PubMed  PubMed Central  Google Scholar 

  • Li KT, Liu DH, Li YL, Chu J, Wang YH, Zhuang YP, Zhang SL (2008) Improved large-scale production of vitamin B12 by Pseudomonas denitrificans with betaine feeding. Bioresour Technol 99(17):8516–8520

    Article  CAS  PubMed  Google Scholar 

  • Lidbury I, Murrell JC, Chen Y (2014) Trimethylamine N-oxide metabolism by abundant marine heterotrophic bacteria. Proc Natl Acad Sci 111(7):2710–2715

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lu WD, Chi ZM, Su CD (2006) Identification of glycine betaine as compatible solute in Synechococcus sp. WH8102 and characterization of its N-methyltransferase genes involved in betaine synthesis. Arch Microbiol 186(6):495–506

    Article  CAS  PubMed  Google Scholar 

  • Luo Y, Lin S, Zhang J, Cooke HA, Bruner SD, Shen B (2008) Regiospecific O-methylation of naphthoic acids catalyzed by NcsB1, an O-methyltransferase involved in the biosynthesis of the enediyne antitumor antibiotic neocarzinostatin. J Biol Chem 283(21):14694–14702

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Meskys R, Harris RJ, Casaite V, Basran J, Scrutton NS (2001) Organization of the genes involved in dimethylglycine and sarcosine degradation in Arthrobacter spp.: implications for glycine betaine catabolism. Eur J Biochem 268(12):3390–3398

    Article  CAS  PubMed  Google Scholar 

  • Millian NS, Garrow TA (1998) Human betaine-homocysteine methyltransferase is a zinc metalloenzyme. Arch Biochem Biophys 356(1):93–98

    Article  CAS  PubMed  Google Scholar 

  • Moore SJ, Lawrence AD, Biedendieck R, Deery E, Frank S, Howard MJ, Rigby SE, Warren MJ (2013) Elucidation of the anaerobic pathway for the corrin component of cobalamin (vitamin B12). Proc Natl Acad Sci 110(37):14906–14911

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Mordukhova EA, Pan JG (2013) Evolved cobalamin-independent methionine synthase (MetE) improves the acetate and thermal tolerance of Escherichia coli. Appl Environ Microbiol 79(24):7905–7915

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Nakagawa Y, Sota M, Koumoto K (2015) Cryoprotective ability of betaine-type metabolite analogs during freezing denaturation of enzymes. Biotechnol Lett 37(8):1607–1613

    Article  CAS  PubMed  Google Scholar 

  • Naughton LM, Blumerman SL, Carlberg M, Boyd EF (2009) Osmoadaptation among vibrio species and unique genomic features and physiological responses of Vibrio parahaemolyticus. Appl Environ Microbiol 75(9):2802–2810

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Naumann E, Hippe H, Gottschalk G (1983) Betaine: new oxidant in the Stickland reaction and methanogenesis from betaine and L-alanine by a Clostridium sporogenes-Methanosarcina barkeri coculture. Appl Environ Microbiol 45:474–483

    CAS  PubMed  PubMed Central  Google Scholar 

  • Nikel PI, Martinez-Garcia E, de Lorenzo V (2014) Biotechnological domestication of pseudomonads using synthetic biology. Nat Rev Microbiol 12(5):368–379

    Article  CAS  PubMed  Google Scholar 

  • Nyyssölä A, Leisola M (2001) Actinopolyspora halophila has two separate pathways for betaine synthesis. Arch Microbiol 176(4):294–300

    Article  PubMed  Google Scholar 

  • Oren A, Elevi Bardavid R, Kandel N, Aizenshtat Z, Jehlicka J (2013) Glycine betaine is the main organic osmotic solute in a stratified microbial community in a hypersaline evaporitic gypsum crust. Extremophiles 17(3):445–451

    Article  CAS  PubMed  Google Scholar 

  • Pacholec M, Tao J, Walsh CT (2005) CouO and NovO: C-methyltransferases for tailoring the aminocoumarin scaffold in coumermycin and novobiocin antibiotic biosynthesis. Biochemistry 44(45):14969–14976

    Article  CAS  PubMed  Google Scholar 

  • Park YI, Buszko ML, Gander JE (1999) Glycine betaine: reserve form of choline in Penicillium fellutanum in low-sulfate medium. Appl Environ Microbiol 65(3):1340–1342

    CAS  PubMed  PubMed Central  Google Scholar 

  • Patallo EP, Blanco G, Fischer C, Brana AF, Rohr J, Mendez C, Salas JA (2001) Deoxysugar methylation during biosynthesis of the antitumor polyketide elloramycin by Streptomyces olivaceus. Characterization of three methyltransferase genes. J Biol Chem 276(22):18765–18774

    Article  CAS  PubMed  Google Scholar 

  • Peter H, Burkovski A, Kramer R (1998) Osmo-sensing by N- and C-terminal extensions of the glycine betaine uptake system BetP of Corynebacterium glutamicum. J Biol Chem 273(5):2567–2574

    Article  CAS  PubMed  Google Scholar 

  • Proctor LM, Lai R, Gunsalus RP (1997) The methanogenic archaeon Methanosarcina thermophila TM-1 possesses a high-affinity glycine betaine transporter involved in osmotic adaptation. Appl Environ Microbiol 63(6):2252–2257

    CAS  PubMed  PubMed Central  Google Scholar 

  • Riekhof WR, Sears BB, Benning C (2005) Annotation of genes involved in glycerolipid biosynthesis in Chlamydomonas reinhardtii: discovery of the betaine lipid synthase BTA1Cr. Eukaryot Cell 4(2):242–252

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Robert H, Le Marrec C, Blanco C, Jebbar M (2000) Glycine betaine, carnitine, and choline enhance salinity tolerance and prevent the accumulation of sodium to a level inhibiting growth of Tetragenococcus halophila. Appl Environ Microbiol 66(2):509–517

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Roeûler M, Mûller K (2001) Osmoadaptation in bacteria and archaea: common principles and differences. Environ Microbiol 3(12):743–754

    Article  Google Scholar 

  • Rönsch H, Kramer R, Morbach S (2003) Impact of osmotic stress on volume regulation, cytoplasmic solute composition and lysine production in Corynebacterium glutamicum MH20-22B. J Biotechnol 104(1–3):87–97

    Article  PubMed  Google Scholar 

  • Sakamoto A, Hayashi H, Tony A, Chen HH, Murata N (2000) Genetic engineering of biosynthesis of glycine betaine enhances tolerance to various stress. In: Cherry JH, Locy RD, Rychter A (ed) Plant tolerance to abiotic stresses in agriculture: role of genetic engineering. Kluwer Academic Publishers, pp 95–104

  • Sarkar M, Pielak GJ (2014) An osmolyte mitigates the destabilizing effect of protein crowding. Protein Sci 23(9):1161–1164

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Schiefner A, Holtmann G, Diederichs K, Welte W, Bremer E (2004) Structural basis for the binding of compatible solutes by ProX from the hyperthermophilic archaeon Archaeoglobus fulgidus. J Biol Chem 279(46):48270–48281

    Article  CAS  PubMed  Google Scholar 

  • Scholz R, Molohon KJ, Nachtigall J, Vater J, Markley AL, Sussmuth RD, Mitchell DA, Borriss R (2011) Plantazolicin, a novel microcin B17/streptolysin S-like natural product from Bacillus amyloliquefaciens FZB42. J Bacteriol 193(1):215–224

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Selmer-Olsen E, Sorhaug T, Birkeland SE, Pehrson R (1999) Survival of Lactobacillus helveticus entrapped in Ca-alginate in relation to water content, storage and rehydration. J Ind Microbiol Biotechnol 23(2):79–85

    Article  CAS  PubMed  Google Scholar 

  • Serra AL, Mariscotti JF, Barra JL, Lucchesi GI, Domenech CE, Lisa AT (2002) Glycine betaine transmethylase mutant of Pseudomonas aeruginosa. J Bacteriol 184(15):4301–4303

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Shintani D, DellaPenna D (1998) Elevating the vitamin E content of plants through metabolic engineering. Science 282(5396):2098–2100

    Article  CAS  PubMed  Google Scholar 

  • Shintani DK, Cheng Z, DellaPenna D (2002) The role of 2-methyl-6-phytylbenzoquinone methyltransferase in determining tocopherol composition in Synechocystis sp. PCC6803. FEBS Lett 511:1–5

    Article  CAS  PubMed  Google Scholar 

  • Smith LT, Pocard JA, Bernard T, Le Rudulier D (1988) Osmotic control of glycine betaine biosynthesis and degradation in Rhizobium meliloti. J Bacteriol 170(7):3142–3149

    CAS  PubMed  PubMed Central  Google Scholar 

  • Steffensky M, Muhlenweg A, Wang ZX, Li SM, Heide L (2000) Identification of the novobiocin biosynthetic gene cluster of Streptomyces spheroides NCIB 11891. Antimicrob Agents Chemother 44(5):1214–1222

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Suzuki H, Tamamura R, Yajima S, Kanno M, Suguro M (2005) Corynebacterium sp. U-96 contains a cluster of genes of enzymes for the catabolism of sarcosine to pyruvate. Biosci Biotechnol Biochem 69(5):952–956

    Article  CAS  PubMed  Google Scholar 

  • Tang MC, Fu CY, Tang GL (2012) Characterization of SfmD as a heme peroxidase that catalyzes the regioselective hydroxylation of 3-methyltyrosine to 3-hydroxy-5-methyltyrosine in saframycin A biosynthesis. J Biol Chem 287(7):5112–5121

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ticak T, Kountz DJ, Girosky KE, Krzycki JA, Ferguson DJ (2014) A nonpyrrolysine member of the widely distributed trimethylamine methyltransferase family is a glycine betaine methyltransferase. Proc Natl Acad Sci 111(43):E4668–E4676

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ticak T, Hariraju D, Arcelay MB, Arivett BA, Fiester SE, Ferguson DJ (2015) Isolation and characterization of a tetramethylammonium-degrading Methanococcoides strain and a novel glycine betaine-utilizing methanolobus strain. Arch Microbiol 197:197–209

    Article  CAS  PubMed  Google Scholar 

  • Underwood SA, Buszko AL, Shanmugam KT, Ingram LO (2004) Lack of protective osmolytes limits final cell density and volumetric productivity of ethanologenic Escherichia coli KO11 during xylose fermentation. Appl Environ Microbiol 70(5):2734–2740

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Vanhauteghem D, Janssens GP, Lauwaerts A, Sys S, Boyen F, Cox E, Meyer E (2013) Exposure to the proton scavenger glycine under alkaline conditions induces Escherichia coli viability loss. PLoS one 8(3):e60328

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Waditee R, Tanaka Y, Aoki K, Hibino T, Jikuya H, Takano J, Takabe T, Takabe T (2003) Isolation and functional characterization of N-methyltransferases that catalyze betaine synthesis from glycine in a halotolerant photosynthetic organism Aphanothece halophytica. J Biol Chem 278(7):4932–4942

    Article  CAS  PubMed  Google Scholar 

  • Wang ZX, Li SM, Heide L (2000) Identification of the coumermycin A(1) biosynthetic gene cluster of Streptomyces rishiriensis DSM 40489. Antimicrob Agents Chemother 44(11):3040–3048

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wargo MJ (2013) Homeostasis and catabolism of choline and glycine betaine: lessons from Pseudomonas aeruginosa. Appl Environ Microbiol 79(7):2112–2120

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Watkins AJ, Roussel EG, Parkes RJ, Sass H (2014) Glycine betaine as a direct substrate for methanogens (Methanococcoides spp.). Appl Environ Microbiol 80(1):289–293

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Xu K, Xu P (2014a) Betaine and beet molasses enhance L-lactic acid production by Bacillus coagulans. PLoS one 9(6):e100731

    Article  PubMed  PubMed Central  Google Scholar 

  • Xu J, Xia X, Zhang J, Guo Y, Zhang W (2014b) An overlooked effect of glycine betaine on fermentation: prevents caramelization and increases the L-lysine production. J Microbiol Biotechnol 24(10):1368–1376

    Article  CAS  PubMed  Google Scholar 

  • Yakimov MM, La Cono V, Slepak VZ, La Spada G, Arcadi E, Messina E, Borghini M, Monticelli LS, Rojo D, Barbas C, Golyshina OV, Ferrer M, Golyshin PN, Giuliano L (2013) Microbial life in the Lake Medee, the largest deep-sea salt-saturated formation. Sci Rep 3:3554

    Article  PubMed  PubMed Central  Google Scholar 

  • Zhang Q, van der Donk WA (2012) Catalytic promiscuity of a bacterial alpha-N-methyltransferase. FEBS Lett 586(19):3391–3397

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zhang J, Cao T, Tang Z, Shen Q, Rosen BP, Zhao FJ (2015) Arsenic methylation and volatilization by arsenite S-adenosylmethionine methyltransferase in Pseudomonas alcaligenes NBRC14159. Appl Environ Microbiol 81(8):2852–2860

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zhou S, Grabar TB, Shanmugam KT, Ingram LO (2006) Betaine tripled the volumetric productivity of D(−)-lactate by Escherichia coli strain SZ132 in mineral salts medium. Biotechnol Lett 28(9):671–676

    Article  CAS  PubMed  Google Scholar 

  • Zhu Y, Eiteman MA, Altman R, Altman E (2008) High glycolytic flux improves pyruvate production by a metabolically engineered Escherichia coli strain. Appl Environ Microbiol 74(21):6649–6655

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zou H, Wu Z, Xian M, Liu H, Cheng T, Cao Y (2013) Not only osmoprotectant: betaine increased lactate dehydrogenase activity and L-lactate production in lactobacilli. Bioresour Technol 148:591–595

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

The present study was supported by the Scientific Research Foundation for the Returned Overseas Chinese Scholars (from State Education Ministry to Huibin Zou), QUST Start-up Fund (from QUST to Huibin Zou), Shandong Province Natural Science Foundation (ZR2015BM011), National Natural Science Foundation (21376129), and Technology Development Project of Shandong Province (2012GNC11307).

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Huibin Zou.

Ethics declarations

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

Conflict of interest

The authors have declared no conflict of interest.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Zou, H., Chen, N., Shi, M. et al. The metabolism and biotechnological application of betaine in microorganism. Appl Microbiol Biotechnol 100, 3865–3876 (2016). https://doi.org/10.1007/s00253-016-7462-3

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00253-016-7462-3

Keywords

Navigation