Skip to main content

Methylobacterium extorquens: methylotrophy and biotechnological applications

Abstract

Methylotrophy is the ability to use reduced one-carbon compounds, such as methanol, as a single source of carbon and energy. Methanol is, due to its availability and potential for production from renewable resources, a valuable feedstock for biotechnology. Nature offers a variety of methylotrophic microorganisms that differ in their metabolism and represent resources for engineering of value-added products from methanol. The most extensively studied methylotroph is the Alphaproteobacterium Methylobacterium extorquens. Over the past five decades, the metabolism of M. extorquens has been investigated physiologically, biochemically, and more recently, using complementary omics technologies such as transcriptomics, proteomics, metabolomics, and fluxomics. These approaches, together with a genome-scale metabolic model, facilitate system-wide studies and the development of rational strategies for the successful generation of desired products from methanol. This review summarizes the knowledge of methylotrophy in M. extorquens, as well as the available tools and biotechnological applications.

This is a preview of subscription content, access via your institution.

Fig. 1
Fig. 2

References

  1. Abanda-Nkpwatt D, Musch M, Tschiersch J, Boettner M, Schwab W (2006) Molecular interaction between Methylobacterium extorquens and seedlings: growth promotion, methanol consumption, and localization of the methanol emission site. J Exp Bot 57:4025–4032

    CAS  PubMed  Article  Google Scholar 

  2. Acharya P, Goenrich M, Hagemeier CH, Demmer U, Vorholt JA, Thauer RK, Ermler U (2005) How an enzyme binds the C1 carrier tetrahydromethanopterin. Structure of the tetrahydromethanopterin-dependent formaldehyde-activating enzyme (Fae) from Methylobacterium extorquens AM1. J Biol Chem 280:13712–13719

    CAS  PubMed  Article  Google Scholar 

  3. Adrio JL, Demain AL (2010) Recombinant organisms for production of industrial products. Bioeng Bugs 1:116–131

    PubMed  Article  Google Scholar 

  4. Alber BE (2011) Biotechnological potential of the ethylmalonyl-CoA pathway. Appl Microbiol Biotechnol 89:17–25

    CAS  PubMed  Article  Google Scholar 

  5. Alber BE, Spanheimer R, Ebenau-Jehle C, Fuchs G (2006) Study of an alternate glyoxylate cycle for acetate assimilation by Rhodobacter sphaeroides. Mol Microbiol 61:297–309

    CAS  PubMed  Article  Google Scholar 

  6. Anderson AJ, Williams DR, Taidi B, Dawes EA, Ewing DF (1992) Studies on copolyester synthesis by Rhodococcus ruber and factors influencing the molecular mass of polyhydroxybutyrate accumulated by Methylobacterium extorquens and Alcaligenes eutrophus. FEMS Microbiol Lett 103:93–101

    CAS  Article  Google Scholar 

  7. Anthony C (1982) The biochemistry of methylotrophs. Academic, London

    Google Scholar 

  8. Anthony C (1986) Bacterial oxidation of methane and methanol. Adv Microb Physiol 27:113–210

    CAS  PubMed  Article  Google Scholar 

  9. Anthony C (1992) The c-type cytochromes of methylotrophic bacteria. Biochim Biophys Acta 1099:1–15

    CAS  PubMed  Article  Google Scholar 

  10. Anthony C (2011) How half a century of research was required to understand bacterial growth on C1 and C2 compounds; the story of the serine cycle and the ethylmalonyl-CoA pathway. Sci Prog 94:109–137

    CAS  PubMed  Article  Google Scholar 

  11. Anthony C, Williams P (2003) The structure and mechanism of methanol dehydrogenase. Biochim Biophys Acta 1647:18–23

    CAS  PubMed  Article  Google Scholar 

  12. Bélanger L, Figueira MM, Bourque D, Morel L, Béland M, Laramée L, Groleau D, Miguez CB (2004) Production of heterologous protein by Methylobacterium extorquens in high cell density fermentation. FEMS Microbiol Lett 231:197–204

    PubMed  Article  CAS  Google Scholar 

  13. Bertau M, Offermanns H, Plass L, Schmidt F, Wernicke H-J (2014) Methanol: the basic chemical and energy feedstock of the future, vol 1. Springer, Heidelberg

    Book  Google Scholar 

  14. Bosch G, Skovran E, Xia Q, Wang T, Taub F, Miller JA, Lidstrom ME, Hackett M (2008) Comprehensive proteomics of Methylobacterium extorquens AM1 metabolism under single carbon and nonmethylotrophic conditions. Proteomics 8:3494–3505

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  15. Bourque D, Ouellette B, André G, Groleau D (1992) Production of poly-β-hydroxybutyrate from methanol: characterization of a new isolate of Methylobacterium extorquens. Appl Microbiol Biotechnol 37:7–12

    CAS  Article  Google Scholar 

  16. Bourque D, Pomerleau Y, Groleau D (1995) High-cell density production of poly-b-hydroxybutyrate (PHB) from methanol by methylobacterium extorquens: production of high-molecular-mass PHB. Appl Microbiol Biotechnol 44:197–204

  17. Bradley AS, Pearson A, Sáenz JP, Marx CJ (2010) Adenosylhopane: the first intermediate in hopanoid side chain biosynthesis. Org Geochem 41:1075–1081

    CAS  Article  Google Scholar 

  18. Caccamo MA, Malone CS, Rasche ME (2004) Biochemical characterization of a dihydromethanopterin reductase involved in tetrahydromethanopterin biosynthesis in Methylobacterium extorquens AM1. J Bacteriol 186:2068–2073

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  19. Carroll SM, Xue KS, Marx CJ (2014) Laboratory divergence of Methylobacterium extorquens AM1 through unintended domestication and past selection for antibiotic resistance. BMC Microbiol 14:2

    PubMed  PubMed Central  Article  CAS  Google Scholar 

  20. Chen G-Q (2009) A microbial polyhydroxyalkanoates (PHA) based bio- and materials industry. Chem Soc Rev 38:2434–2446

    CAS  PubMed  Article  Google Scholar 

  21. Chistoserdov AY, Chistoserdova LV, McIntire WS, Lidstrom ME (1994) Genetic organization of the mau gene cluster in Methylobacterium extorquens AM1: complete nucleotide sequence and generation and characteristics of mau mutants. J Bacteriol 176:4052–4065

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  22. Chistoserdova L (2011) Modularity of methylotrophy, revisited. Environ Microbiol 13:2603–2622

    CAS  PubMed  Article  Google Scholar 

  23. Chistoserdova LV, Lidstrom ME (1992) Cloning, mutagenesis, and physiological effect of a hydroxypyruvate reductase gene from Methylobacterium extorquens AM1. J Bacteriol 174:71–77

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  24. Chistoserdova L, Lidstrom ME (1997) Molecular and mutational analysis of a DNA region separating two methylotrophy gene clusters in Methylobacterium extorquens AM1. Microbiology 143(Pt 5):1729–1736

    CAS  PubMed  Article  Google Scholar 

  25. Chistoserdova L, Lidstrom M (2013) Aerobic methylotrophic prokaryotes. In: Rosenberg E, DeLong EF, Thompson F, Lory S, Stackebrandt E (eds) The prokaryotes, 4th edn. Springer, New York, pp 267–285

    Chapter  Google Scholar 

  26. Chistoserdova L, Vorholt JA, Thauer RK, Lidstrom ME (1998) C1 transfer enzymes and coenzymes linking methylotrophic bacteria and methanogenic Archaea. Science 281:99–102

    CAS  PubMed  Article  Google Scholar 

  27. Chistoserdova L, Chen SW, Lapidus A, Lidstrom ME (2003) Methylotrophy in Methylobacterium extorquens AM1 from a genomic point of view. J Bacteriol 185:2980–2987

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  28. Chistoserdova L, Laukel M, Portais JC, Vorholt JA, Lidstrom ME (2004) Multiple formate dehydrogenase enzymes in the facultative methylotroph Methylobacterium extorquens AM1 are dispensable for growth on methanol. J Bacteriol 186:22–28

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  29. Chistoserdova L, Rasche ME, Lidstrom ME (2005a) Novel dephosphotetrahydromethanopterin biosynthesis genes discovered via mutagenesis in Methylobacterium extorquens AM1. J Bacteriol 187:2508–2512

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  30. Chistoserdova L, Vorholt JA, Lidstrom ME (2005b) A genomic view of methane oxidation by aerobic bacteria and anaerobic archaea. Genome Biol 6:208

    PubMed  PubMed Central  Article  Google Scholar 

  31. Chistoserdova L, Crowther GJ, Vorholt JA, Skovran E, Portais JC, Lidstrom ME (2007) Identification of a fourth formate dehydrogenase in Methylobacterium extorquens AM1 and confirmation of the essential role of formate oxidation in methylotrophy. J Bacteriol 189:9076–9081

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  32. Choi YJ, Morel L, Bourque D, Mullick A, Massie B, Miguez CB (2006) Bestowing inducibility on the cloned methanol dehydrogenase promoter (PmxaF) of Methylobacterium extorquens by applying regulatory elements of Pseudomonas putida F1. Appl Environ Microbiol 72:7723–7729

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  33. Choi YJ, Gringorten JL, Belanger L, Morel L, Bourque D, Masson L, Groleau D, Miguez CB (2008) Production of an insecticidal crystal protein from Bacillus thuringiensis by the methylotroph Methylobacterium extorquens. Appl Environ Microbiol 74:5178–5182

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  34. Chou HH, Marx CJ (2012) Optimization of gene expression through divergent mutational paths. Cel Rep 1:133–140

    CAS  Article  Google Scholar 

  35. Chou H-H, Berthet J, Marx CJ (2009) Fast growth increases the selective advantage of a mutation arising recurrently during evolution under metal limitation. PLoS Genet 5:e1000652

    PubMed  PubMed Central  Article  CAS  Google Scholar 

  36. Chubiz LM, Purswani J, Carroll SM, Marx CJ (2013) A novel pair of inducible expression vectors for use in Methylobacterium extorquens. BMC Res Notes 6:183

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  37. Crowther GJ, Kosaly G, Lidstrom ME (2008) Formate as the main branch point for methylotrophic metabolism in Methylobacterium extorquens AM1. J Bacteriol 190:5057–5062

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  38. Dedysh SN, Dunfield PF, Trotsenko YA (2004) Methane utilization by Methylobacterium species: new evidence but still no proof for an old controversy. Int J Syst Evol Microbiol 54:1919–1920

    PubMed  Article  Google Scholar 

  39. Delaney NF, Kaczmarek ME, Ward LM, Swanson PK, Lee MC, Marx CJ (2013) Development of an optimized medium, strain and high-throughput culturing methods for Methylobacterium extorquens. PLoS One 8:e62957

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  40. Delmotte N, Knief C, Chaffron S, Innerebner G, Roschitzki B, Schlapbach R, von Mering C, Vorholt JA (2009) Community proteogenomics reveals insights into the physiology of phyllosphere bacteria. Proc Natl Acad Sci U S A 106:16428–16433

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  41. Doronina NVSA, Trotsenko YA (1996) Isolation and initial characterization of aerobic chloromethane-utilizing bacteria. FEMS Microbiol Lett 179–183

  42. Dunstan PM, Anthony C (1973) Microbial metabolism of C1 and C2 compounds. The role of acetate during growth of Pseudomonas AM1 on C1 compounds, ethanol and β-hydroxybutyrate. Biochem J 132:797–801

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  43. Dunstan PM, Anthony C, Drabble WT (1972) Microbial metabolism of C1 and C2 compounds. The role of glyoxylate, glycollate and acetate in the growth of Pseudomonas AM1 on ethanol and on C1 compounds. Biochem J 128:107–115

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  44. Erb TJ, Berg IA, Brecht V, Muller M, Fuchs G, Alber BE (2007) Synthesis of C5-dicarboxylic acids from C2-units involving crotonyl-CoA carboxylase/reductase: the ethylmalonyl-CoA pathway. Proc Natl Acad Sci U S A 104:10631–10636

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  45. Erb TJ, Retey J, Fuchs G, Alber BE (2008) Ethylmalonyl-CoA mutase from Rhodobacter sphaeroides defines a new subclade of coenzyme B12-dependent acyl-CoA mutases. J Biol Chem 283:32283–32293

    CAS  PubMed  Article  Google Scholar 

  46. Ermler U, Hagemeier CH, Roth A, Demmer U, Grabarse W, Warkentin E, Vorholt JA (2002) Structure of methylene-tetrahydromethanopterin dehydrogenase from Methylobacterium extorquens AM1. Structure 10:1127–1137

    CAS  PubMed  Article  Google Scholar 

  47. Escalante-Semerena JC, Rinehart KL Jr, Wolfe RS (1984) Tetrahydromethanopterin, a carbon carrier in methanogenesis. J Biol Chem 259:9447–9455

    CAS  PubMed  Google Scholar 

  48. Ettwig KF, Butler MK, Le Paslier D, Pelletier E, Mangenot S, Kuypers MM, Schreiber F, Dutilh BE, Zedelius J, de Beer D, Gloerich J, Wessels HJ, van Alen T, Luesken F, Wu ML, van de Pas-Schoonen KT, Op den Camp HJ, Janssen-Megens EM, Francoijs KJ, Stunnenberg H, Weissenbach J, Jetten MS, Strous M (2010) Nitrite-driven anaerobic methane oxidation by oxygenic bacteria. Nature 464:543–548

    CAS  PubMed  Article  Google Scholar 

  49. Fall R, Benson AA (1996) Leaf methanol—the simplest natural product from plants. Trends Plant Sci 1:296–301

    Article  Google Scholar 

  50. Fedorov DN, Doronina NV, Trotsenko Iu A (2011) Phytosymbiosis of aerobic methylobacteria: new facts and views. Mikrobiologiia 80:435–446

    CAS  PubMed  Google Scholar 

  51. Ferrer-Miralles N, Domingo-Espin J, Corchero J, Vazquez E, Villaverde A (2009) Microbial factories for recombinant pharmaceuticals. Microb Cell Fact 8:17

    PubMed  PubMed Central  Article  CAS  Google Scholar 

  52. Figueira MM, Laramee L, Murrell JC, Groleau D, Miguez CB (2000) Production of green fluorescent protein by the methylotrophic bacterium Methylobacterium extorquens. FEMS Microbiol Lett 193:195–200

    CAS  PubMed  Article  Google Scholar 

  53. Fitzgerald KA, Lidstrom ME (2003) Overexpression of a heterologous protein, haloalkane dehalogenase, in a poly-β-hydroxybutyrate-deficient strain of the facultative methylotroph Methylobacterium extorquens AM1. Biotechnol Bioeng 81:263–268

    CAS  PubMed  Article  Google Scholar 

  54. Gao X, Wang P, Tang Y (2010) Engineered polyketide biosynthesis and biocatalysis in Escherichia coli. Appl Microbiol Biotechnol 88:1233–1242

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  55. Goodman M (2009) Market watch: sales of biologics to show robust growth through to 2013. Nat Rev Drug Discov 8:837

    CAS  PubMed  Article  Google Scholar 

  56. Group F (2009) World enzymes to 2013. The Freedonia Group, Inc, Cleveland

  57. Gruffaz C, Muller EE, Louhichi-Jelail Y, Nelli YR, Guichard G, Bringel F (2014) Genes of the N-methylglutamate pathway are essential for growth of Methylobacterium extorquens DM4 with monomethylamine. Appl Environ Microbiol 80:3541–3550

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  58. Guo X, Lidstrom ME (2006) Physiological analysis of Methylobacterium extorquens AM1 grown in continuous and batch cultures. Arch Microbiol 186:139–149

    CAS  PubMed  Article  Google Scholar 

  59. Guo X, Lidstrom ME (2008) Metabolite profiling analysis of Methylobacterium extorquens AM1 by comprehensive two-dimensional gas chromatography coupled with time-of-flight mass spectrometry. Biotechnol Bioeng 99:929–940

    CAS  PubMed  Article  Google Scholar 

  60. Gutierrez J, Bourque D, Criado R, Choi YJ, Cintas LM, Hernandez PE, Miguez CB (2005) Heterologous extracellular production of enterocin P from Enterococcus faecium P13 in the methylotrophic bacterium Methylobacterium extorquens. FEMS Microbiol Lett 248:125–131

    CAS  PubMed  Article  Google Scholar 

  61. Hagemeier CH, Chistoserdova L, Lidstrom ME, Thauer RK, Vorholt JA (2000) Characterization of a second methylene tetrahydromethanopterin dehydrogenase from Methylobacterium extorquens AM1. Eur J Biochem 267:3762–3769

    CAS  PubMed  Article  Google Scholar 

  62. Hagishita T, Yoshida T, Izumi Y, Mitsunaga T (1996) Efficient L-serine production from methanol and glycine by resting cells of Methylobacterium sp. strain MN43. Biosci Biotechnol Biochem 60:1604–1607

    CAS  PubMed  Article  Google Scholar 

  63. Heptinstall J, Quayle JR (1970) Pathways leading to and from serine during growth of Pseudomonas AM1 on C1 compounds or succinate. Biochem J 117:563–572

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  64. Hofer P, Choi YJ, Osborne MJ, Miguez CB, Vermette P, Groleau D (2010) Production of functionalized polyhydroxyalkanoates by genetically modified Methylobacterium extorquens strains. Microb Cell Fact 9:70

    PubMed  PubMed Central  Article  CAS  Google Scholar 

  65. Hu B, Lidstrom M (2012) CcrR, a TetR family transcriptional regulator, activates the transcription of a gene of the ethylmalonyl coenzyme A pathway in Methylobacterium extorquens AM1. J Bacteriol 194:2802–2808

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  66. Hu B, Lidstrom M (2014) Metabolic engineering of Methylobacterium extorquens AM1 for 1-butanol production. Biotechnol Biofuels 7:156

    PubMed  PubMed Central  Article  CAS  Google Scholar 

  67. Ikeda M (2003) Amino acid production processes. Adv Biochem Eng Biotechnol 79:1–35

    CAS  PubMed  Google Scholar 

  68. Joe MM, Saravanan VS, Islam MR, Sa T (2013) Development of alginate-based aggregate inoculants of Methylobacterium sp. and Azospirillum brasilense tested under in vitro conditions to promote plant growth. J Appl Microbiol. doi: 10.1111/jam.12384

  69. Kaczmarczyk A, Vorholt JA, Francez-Charlot A (2013) Cumate-inducible gene expression system for sphingomonads and other Alphaproteobacteria. Appl Environ Microbiol 79:6795–6802

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  70. Kalyuzhnaya MG, Lidstrom ME (2003) QscR, a LysR-type transcriptional regulator and CbbR homolog, is involved in regulation of the serine cycle genes in Methylobacterium extorquens AM1. J Bacteriol 185:1229–1235

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  71. Kalyuzhnaya MG, Lidstrom ME (2005) QscR-mediated transcriptional activation of serine cycle genes in Methylobacterium extorquens AM1. J Bacteriol 187:7511–7517

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  72. Keshavarz T, Roy I (2010) Polyhydroxyalkanoates: bioplastics with a green agenda. Curr Opin Microbiol 13:321–326

    CAS  PubMed  Article  Google Scholar 

  73. Khosravi-Darani K, Mokhtari Z-B, Amai T, Tanaka K (2013) Microbial production of poly(hydroxybutyrate) from C1 carbon sources. Appl Microbiol Biotechnol 97:1407–1424

    CAS  PubMed  Article  Google Scholar 

  74. Kiefer P, Portais JC, Vorholt JA (2008) Quantitative metabolome analysis using liquid chromatography-high-resolution mass spectrometry. Anal Biochem 382:94–100

    CAS  PubMed  Article  Google Scholar 

  75. Kiefer P, Buchhaupt M, Christen P, Kaup B, Schrader J, Vorholt JA (2009) Metabolite profiling uncovers plasmid-induced cobalt limitation under methylotrophic growth conditions. PLoS One 4:e7831

    PubMed  PubMed Central  Article  CAS  Google Scholar 

  76. Kiefer P, Delmotte N, Vorholt JA (2011) Nanoscale ion-pair reversed-phase HPLC-MS for sensitive metabolome analysis. Anal Chem 83:850–855

    CAS  PubMed  Article  Google Scholar 

  77. Knief C, Frances L, Vorholt JA (2010) Competitiveness of diverse Methylobacterium strains in the phyllosphere of Arabidopsis thaliana and identification of representative models, including M. extorquens PA1. Microb Ecol 60:440–452

    PubMed  Article  Google Scholar 

  78. Kohler-Staub DH, Hartmans S, Gälli R, Suter F, Leisinger T (1986) Evidence for identical dichloromethane dehalogenases in different methylotrophic bacteria. J Gen Microbiol 2837–2843

  79. Kornberg HL, Krebs HA (1957) Synthesis of cell constituents from C2-units by a modified tricarboxylic acid cycle. Nature 179:988–991

    CAS  PubMed  Article  Google Scholar 

  80. Korotkova N, Lidstrom ME (2001) Connection between poly-β-hydroxybutyrate biosynthesis and growth on C1 and C2 compounds in the methylotroph Methylobacterium extorquens AM1. J Bacteriol 183:1038–1046

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  81. Korotkova N, Chistoserdova L, Kuksa V, Lidstrom ME (2002a) Glyoxylate regeneration pathway in the methylotroph Methylobacterium extorquens AM1. J Bacteriol 184:1750–1758

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  82. Korotkova N, Chistoserdova L, Lidstrom ME (2002b) Poly-β-hydroxybutyrate biosynthesis in the facultative methylotroph Methylobacterium extorquens AM1: identification and mutation of gap11, gap20, and phaR. J Bacteriol 184:6174–6181

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  83. Korotkova N, Lidstrom ME, Chistoserdova L (2005) Identification of genes involved in the glyoxylate regeneration cycle in Methylobacterium extorquens AM1, including two new genes, meaC and meaD. J Bacteriol 187:1523–1526

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  84. Large PJ, Quayle JR (1963) Microbial growth on C1 compounds. 5. Enzyme activities in extracts of Pseudomonas AM1. Biochem J 87:386–396

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  85. Large PJ, Peel D, Quayle JR (1961) Microbial growth on C1 compounds. 2. Synthesis of cell constituents by methanol- and formate-grown Pseudomonas AM 1, and methanol-grown Hyphomicrobium vulgare. Biochem J 81:470–480

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  86. Large PJ, Peel D, Quayle JR (1962a) Microbial growth on C1 compounds. 3. Distribution of radioactivity in metabolites of methanol-grown Pseudomonas AM1 after incubation with [14C]methanol and [14C]bicarbonate. Biochem J 82:483–488

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  87. Large PJ, Peel D, Quayle JR (1962b) Microbial growth on C1 compounds. 4. Carboxylation of phosphoenolpyruvate in methanol-grown Pseudomonas AM1. Biochem J 85:243–250

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  88. Laukel M, Chistoserdova L, Lidstrom ME, Vorholt JA (2003) The tungsten-containing formate dehydrogenase from Methylobacterium extorquens AM1: purification and properties. Eur J Biochem 270:325–333

    CAS  PubMed  Article  Google Scholar 

  89. Laukel M, Rossignol M, Borderies G, Volker U, Vorholt JA (2004) Comparison of the proteome of Methylobacterium extorquens AM1 grown under methylotrophic and nonmethylotrophic conditions. Proteomics 4:1247–1264

    CAS  PubMed  Article  Google Scholar 

  90. Lee MC, Chou HH, Marx CJ (2009) Asymmetric, bimodal trade-offs during adaptation of Methylobacterium to distinct growth substrates. Evolution 63:2816–2830

    CAS  PubMed  Article  Google Scholar 

  91. Leisinger T, Bader R, Hermann R, Schmid-Appert M, Vuilleumier S (1994) Microbes, enzymes and genes involved in dichloromethane utilization. Biodegradation 5:237–248

    CAS  PubMed  Article  Google Scholar 

  92. Macauley-Patrick S, Fazenda ML, McNeil B, Harvey LM (2005) Heterologous protein production using the Pichia pastoris expression system. Yeast 22:249–270

    CAS  PubMed  Article  Google Scholar 

  93. Maden BE (2000) Tetrahydrofolate and tetrahydromethanopterin compared: functionally distinct carriers in C1 metabolism. Biochem J 350(Pt 3):609–629

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  94. Martinez-Gomez NC, Nguyen S, Lidstrom ME (2013) Elucidation of the role of the methylene-tetrahydromethanopterin dehydrogenase MtdA in the tetrahydromethanopterin-dependent oxidation pathway in Methylobacterium extorquens AM1. J Bacteriol 195:2359–2367

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  95. Marx CJ (2008) Development of a broad-host-range sacB-based vector for unmarked allelic exchange. BMC Res Notes 1:1

    PubMed  PubMed Central  Article  CAS  Google Scholar 

  96. Marx CJ, Lidstrom ME (2001) Development of improved versatile broad-host-range vectors for use in methylotrophs and other Gram-negative bacteria. Microbiology 147:2065–2075

    CAS  PubMed  Article  Google Scholar 

  97. Marx CJ, Lidstrom ME (2002) Broad-host-range cre-lox system for antibiotic marker recycling in gram-negative bacteria. Biotechniques 33:1062–1067

    CAS  PubMed  Google Scholar 

  98. Marx CJ, Lidstrom ME (2004) Development of an insertional expression vector system for Methylobacterium extorquens AM1 and generation of null mutants lacking mtdA and/or fch. Microbiology 150:9–19

    CAS  PubMed  Article  Google Scholar 

  99. Marx CJ, Chistoserdova L, Lidstrom ME (2003a) Formaldehyde-detoxifying role of the tetrahydromethanopterin-linked pathway in Methylobacterium extorquens AM1. J Bacteriol 185:7160–7168

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  100. Marx CJ, Laukel M, Vorholt JA, Lidstrom ME (2003b) Purification of the formate-tetrahydrofolate ligase from Methylobacterium extorquens AM1 and demonstration of its requirement for methylotrophic growth. J Bacteriol 185:7169–7175

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  101. Marx CJ, O’Brien BN, Breezee J, Lidstrom ME (2003c) Novel methylotrophy genes of Methylobacterium extorquens AM1 identified by using transposon mutagenesis including a putative dihydromethanopterin reductase. J Bacteriol 185:669–673

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  102. Marx CJ, Van Dien SJ, Lidstrom ME (2005) Flux analysis uncovers key role of functional redundancy in formaldehyde metabolism. PLoS Biol 3:e16

    PubMed  PubMed Central  Article  CAS  Google Scholar 

  103. Marx CJ, Bringel F, Chistoserdova L, Moulin L, Farhan Ul Haque M, Fleischman DE, Gruffaz C, Jourand P, Knief C, Lee MC, Muller EE, Nadalig T, Peyraud R, Roselli S, Russ L, Goodwin LA, Ivanova N, Kyrpides N, Lajus A, Land ML, Medigue C, Mikhailova N, Nolan M, Woyke T, Stolyar S, Vorholt JA, Vuilleumier S (2012) Complete genome sequences of six strains of the genus Methylobacterium. J Bacteriol 194:4746–4748

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  104. McMahon MD, Prather KL (2014) Functional screening and in vitro analysis reveal thioesterases with enhanced substrate specificity profiles that improve short-chain fatty acid production in Escherichia coli. Appl Environ Microbiol 80:1042–1050

    PubMed  PubMed Central  Article  CAS  Google Scholar 

  105. Meister M, Saum S, Alber BE, Fuchs G (2005) L-Malyl-coenzyme A/β-methylmalyl-coenzyme A lyase is involved in acetate assimilation of the isocitrate lyase-negative bacterium Rhodobacter capsulatus. J Bacteriol 187:1415–1425

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  106. Metzger LC, Francez-Charlot A, Vorholt JA (2013) Single-domain response regulator involved in the general stress response of Methylobacterium extorquens. Microbiology 159:1067–1076

    CAS  PubMed  Article  Google Scholar 

  107. Mokhtari-Hosseini ZB, Vasheghani-Farahani E, Shojaosadati SA, Karimzadeh R, Heidarzadeh-Vazifekhoran A (2009) Effect of feed composition on PHB production from methanol by HCDC of Methylobacterium extorquens (DSMZ 1340). J Chem Technol Biotechnol 84:1136–1139

    CAS  Article  Google Scholar 

  108. Morris CJ, Lidstrom ME (1992) Cloning of a methanol-inducible moxF promoter and its analysis in moxB mutants of Methylobacterium extorquens AM1rif. J Bacteriol 174:4444–4449

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  109. Morris CJ, Biville F, Turlin E, Lee E, Ellermann K, Fan WH, Ramamoorthi R, Springer AL, Lidstrom ME (1994) Isolation, phenotypic characterization, and complementation analysis of mutants of Methylobacterium extorquens AM1 unable to synthesize pyrroloquinoline quinone and sequences of pqqD, pqqG, and pqqC. J Bacteriol 176:1746–1755

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  110. Morris CJ, Kim YM, Perkins KE, Lidstrom ME (1995) Identification and nucleotide sequences of mxaA, mxaC, mxaK, mxaL, and mxaD genes from Methylobacterium extorquens AM1. J Bacteriol 177:6825–6831

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  111. Muller EE, Hourcade E, Louhichi-Jelail Y, Hammann P, Vuilleumier S, Bringel F (2011) Functional genomics of dichloromethane utilization in Methylobacterium extorquens DM4. Environ Microbiol 13:2518–2535

    CAS  PubMed  Article  Google Scholar 

  112. Müller JE, Heggeset TMB, Wendisch VF, Vorholt JA, Brautaset T (2014) Methylotrophy in the thermophilic Bacillus methanolicus, basic insights and application for commodity productions from methanol. Appl Microbiol Biotechnol doi:10.1007/s00253-014-6224-3

  113. Nakagawa T, Mitsui R, Tani A, Sasa K, Tashiro S, Iwama T, Hayakawa T, Kawai K (2012) A catalytic role of XoxF1 as La3+-dependent methanol dehydrogenase in Methylobacterium extorquens strain AM1. PLoS One 7:e50480

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  114. Nayak DD, Marx CJ (2014a) Genetic and phenotypic comparison of facultative methylotrophy between Methylobacterium extorquens strains PA1 and AM1. PLoS One 9:e107887

    PubMed  PubMed Central  Article  CAS  Google Scholar 

  115. Nayak DD, Marx CJ (2014b) Methylamine utilization via the N-methylglutamate pathway in Methylobacterium extorquens PA1 involves a novel flow of carbon through C1 assimilation and dissimilation pathways. J Bacteriol 196:4130–4139

    PubMed  PubMed Central  Article  CAS  Google Scholar 

  116. Nunn DN, Lidstrom ME (1986) Isolation and complementation analysis of 10 methanol oxidation mutant classes and identification of the methanol dehydrogenase structural gene of Methylobacterium sp. strain AM1. J Bacteriol 166:581–590

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  117. Okubo Y, Skovran E, Guo X, Sivam D, Lidstrom ME (2007) Implementation of microarrays for Methylobacterium extorquens AM1. OMICS 11:325–340

    PubMed  Article  CAS  Google Scholar 

  118. Olah GA (2013) Towards oil independence through renewable methanol chemistry. Angew Chem Int Ed 52:104–107

    CAS  Article  Google Scholar 

  119. Orita I, Nishikawa K, Nakamura S, Fukui T (2014) Biosynthesis of polyhydroxyalkanoate copolymers from methanol by Methylobacterium extorquens AM1 and the engineered strains under cobalt-deficient conditions. Appl Microbiol Biotechnol 98:3715–3725

    CAS  PubMed  Article  Google Scholar 

  120. Panda AK (2003) Bioprocessing of therapeutic proteins from the inclusion bodies of Escherichia coli. Adv Biochem Eng Biotechnol 85:43–93

    CAS  PubMed  Google Scholar 

  121. Peel D, Quayle JR (1961) Microbial growth on C1 compounds. 1. Isolation and characterization of Pseudomonas AM 1. Biochem J 81:465–469

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  122. Peralta-Yahya PP, Zhang F, del Cardayre SB, Keasling JD (2012) Microbial engineering for the production of advanced biofuels. Nature 488:320–328

    CAS  PubMed  Article  Google Scholar 

  123. Peyraud R, Kiefer P, Christen P, Massou S, Portais JC, Vorholt JA (2009) Demonstration of the ethylmalonyl-CoA pathway by using 13C metabolomics. Proc Natl Acad Sci U S A 106:4846–4851

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  124. Peyraud R, Schneider K, Kiefer P, Massou S, Vorholt JA, Portais JC (2011) Genome-scale reconstruction and system level investigation of the metabolic network of Methylobacterium extorquens AM1. BMC Syst Biol 5:189

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  125. Peyraud R, Kiefer P, Christen P, Portais JC, Vorholt JA (2012) Co-consumption of methanol and succinate by Methylobacterium extorquens AM1. PLoS One 7:e48271

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  126. Pfeifer BA, Khosla C (2001) Biosynthesis of polyketides in heterologous hosts. Microbiol Mol Biol R 65:106–118

    CAS  Article  Google Scholar 

  127. Pomper BK, Vorholt JA (2001) Characterization of the formyltransferase from Methylobacterium extorquens AM1. Eur J Biochem 268:4769–4775

    CAS  PubMed  Article  Google Scholar 

  128. Pomper BK, Vorholt JA, Chistoserdova L, Lidstrom ME, Thauer RK (1999) A methenyl tetrahydromethanopterin cyclohydrolase and a methenyl tetrahydrofolate cyclohydrolase in Methylobacterium extorquens AM1. Eur J Biochem 261:475–480

    CAS  PubMed  Article  Google Scholar 

  129. Pomper BK, Saurel O, Milon A, Vorholt JA (2002) Generation of formate by the formyltransferase/hydrolase complex (Fhc) from Methylobacterium extorquens AM1. FEBS Lett 523:133–137

    CAS  PubMed  Article  Google Scholar 

  130. Rasche ME, Havemann SA, Rosenzvaig M (2004) Characterization of two methanopterin biosynthesis mutants of Methylobacterium extorquens AM1 by use of a tetrahydromethanopterin bioassay. J Bacteriol 186:1565–1570

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  131. Richardson IW, Anthony C (1992) Characterization of mutant forms of the quinoprotein methanol dehydrogenase lacking an essential calcium ion. Biochem J 287(Pt 3):709–715

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  132. Roselli S, Nadalig T, Vuilleumier S, Bringel F (2013) The 380 kb pCMU01 plasmid encodes chloromethane utilization genes and redundant genes for vitamin B12- and tetrahydrofolate-dependent chloromethane metabolism in Methylobacterium extorquens CM4: a proteomic and bioinformatics study. PLoS One 8:e56598

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  133. Sanchez S, Demain AL (2008) Metabolic regulation and overproduction of primary metabolites. Microb Biotechnol 1:283–319

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  134. Schada von Borzyskowski L, Remus-Emsermann M, Weishaupt R, Vorholt JA, Erb TJ (2014) A set of versatile brick vectors and promoters for the assembly, expression, and integration of synthetic operons in Methylobacterium extorquens AM1 and other Alphaproteobacteria. ACS Synth Biol. doi: 10.1021/sb500221v

  135. Schmidt S, Christen P, Kiefer P, Vorholt JA (2010) Functional investigation of methanol dehydrogenase-like protein XoxF in Methylobacterium extorquens AM1. Microbiology 156:2575–2586

    CAS  PubMed  Article  Google Scholar 

  136. Schneider K, Peyraud R, Kiefer P, Christen P, Delmotte N, Massou S, Portais JC, Vorholt JA (2012a) The ethylmalonyl-CoA pathway is used in place of the glyoxylate cycle by Methylobacterium extorquens AM1 during growth on acetate. J Biol Chem 287:757–766

    CAS  PubMed  Article  Google Scholar 

  137. Schneider K, Skovran E, Vorholt JA (2012b) Oxalyl-coenzyme A reduction to glyoxylate is the preferred route of oxalate assimilation in Methylobacterium extorquens AM1. J Bacteriol 194:3144–3155

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  138. Schrader J, Schilling M, Holtmann D, Sell D, Filho MV, Marx A, Vorholt JA (2009) Methanol-based industrial biotechnology: current status and future perspectives of methylotrophic bacteria. Trends Biotechnol 27:107–115

    CAS  PubMed  Article  Google Scholar 

  139. Senior PJ, Windass J (1980) The ICI single cell protein process. Biotechnol Lett 2:205–210

    CAS  Article  Google Scholar 

  140. Sirirote P, Yamane T, Shimizu S (1986) Production of L-serine from methanol and glycine by resting cells of a methylotroph under automatically controlled conditions. J Ferment Technol 64:389–396

    CAS  Article  Google Scholar 

  141. Sirirote P, Tsuneo Y, Shoichi S (1988) L-serine production from methanol and glycine with an immobilized methylotroph. J Ferment Technol 66:291–297

    CAS  Article  Google Scholar 

  142. Skovran E, Crowther GJ, Guo X, Yang S, Lidstrom ME (2010) A systems biology approach uncovers cellular strategies used by Methylobacterium extorquens AM1 during the switch from multi- to single-carbon growth. PLoS One 5:e14091

    PubMed  PubMed Central  Article  CAS  Google Scholar 

  143. Skovran E, Palmer AD, Rountree AM, Good NM, Lidstrom ME (2011) XoxF is required for expression of methanol dehydrogenase in Methylobacterium extorquens AM1. J Bacteriol 193:6032–6038

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  144. Smejkalova H, Erb TJ, Fuchs G (2010) Methanol assimilation in Methylobacterium extorquens AM1: demonstration of all enzymes and their regulation. PLoS One 5:e13001

  145. Sonntag F, Buchhaupt M, Schrader J (2014) Thioesterases for ethylmalonyl-CoA pathway derived dicarboxylic acid production in Methylobacterium extorquens AM1. Appl Microbiol Biotechnol 98(10):4533−4544

  146. Springer AL, Chou HH, Fan WH, Lee E, Lidstrom ME (1995) Methanol oxidation mutants in Methylobacterium extorquens AM1: identification of new genetic complementation groups. Microbiology 141(Pt 11):2985–2993

    CAS  PubMed  Article  Google Scholar 

  147. Springer AL, Morris CJ, Lidstrom ME (1997) Molecular analysis of mxbD and mxbM, a putative sensor-regulator pair required for oxidation of methanol in Methylobacterium extorquens AM1. Microbiology 143(Pt 5):1737–1744

    CAS  PubMed  Article  Google Scholar 

  148. Springer AL, Auman AJ, Lidstrom ME (1998) Sequence and characterization of mxaB, a response regulator involved in regulation of methanol oxidation, and of mxaW, a methanol-regulated gene in Methylobacterium extorquens AM1. FEMS Microbiol Lett 160:119–124

    CAS  PubMed  Article  Google Scholar 

  149. Stolz M, Peters-Wendisch P, Etterich H, Gerharz T, Faurie R, Sahm H, Fersterra H, Eggeling L (2007) Reduced folate supply as a key to enhanced L-serine production by Corynebacterium glutamicum. Appl Environ Microbiol 73:750–755

    CAS  PubMed  Article  Google Scholar 

  150. Studer A, Stupperich E, Vuilleumier S, Leisinger T (2001) Chloromethane: tetrahydrofolate methyl transfer by two proteins from Methylobacterium chloromethanicum strain CM4. Eur J Biochem 268:2931–2938

    CAS  PubMed  Article  Google Scholar 

  151. Studer A, McAnulla C, Buchele R, Leisinger T, Vuilleumier S (2002) Chloromethane-induced genes define a third C1 utilization pathway in Methylobacterium chloromethanicum CM4. J Bacteriol 184:3476–3484

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  152. Suzuki T, Yamane T, Shimizu S (1986) Mass production of poly-β-hydroxybutyric acid by fully automatic fed-batch culture of methylotroph. Appl Microbiol Biotechnol 23:322–329

    CAS  Article  Google Scholar 

  153. Sy A, Timmers AC, Knief C, Vorholt JA (2005) Methylotrophic metabolism is advantageous for Methylobacterium extorquens during colonization of Medicago truncatula under competitive conditions. Appl Environ Microbiol 71:7245–7252

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  154. Taidi B, Anderson A, Dawes E, Byrom D (1994) Effect of carbon source and concentration on the molecular mass of poly(3-hydroxybutyrate) produced by Methylobacterium extorquens and Alcaligenes eutrophus. Appl Microbiol Biotechnol 40:786–790

    CAS  Article  Google Scholar 

  155. Tani A, Takai Y, Suzukawa I, Akita M, Murase H, Kimbara K (2012) Practical application of methanol-mediated mutualistic symbiosis between Methylobacterium species and a roof greening moss, Racomitrium japonicum. PLoS One 7:e33800

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  156. Thauer RK (1998) Biochemistry of methanogenesis: a tribute to Marjory Stephenson. Microbiology 144(Pt 9):2377–2406

    CAS  PubMed  Article  Google Scholar 

  157. Toyama H, Chistoserdova L, Lidstrom ME (1997) Sequence analysis of pqq genes required for biosynthesis of pyrroloquinoline quinone in Methylobacterium extorquens AM1 and the purification of a biosynthetic intermediate. Microbiology 143(Pt 2):595–602

    CAS  PubMed  Article  Google Scholar 

  158. Ueda S, Matsumoto S, Takagi A, Yamane T (1992) Synthesis of poly(3-hydroxybutyrate-Co-3-hydroxyvalerate) from methanol and n-amyl alcohol by the methylotrophic bacteria Paracoccus denitrificans and Methylobacterium extorquens. Appl Environ Microbiol 58:3574–3579

    CAS  PubMed  PubMed Central  Google Scholar 

  159. Van Aken B, Peres CM, Doty SL, Yoon JM, Schnoor JL (2004) Methylobacterium populi sp. nov., a novel aerobic, pink-pigmented, facultatively methylotrophic, methane-utilizing bacterium isolated from poplar trees (Populus deltoides × nigra DN34). Int J Syst Evol Microbiol 54:1191–1196

    PubMed  Article  CAS  Google Scholar 

  160. Van Dien SJ, Strovas T, Lidstrom ME (2003) Quantification of central metabolic fluxes in the facultative methylotroph Methylobacterium extorquens AM1 using 13C-label tracing and mass spectrometry. Biotechnol Bioeng 84:45–55

    PubMed  Article  CAS  Google Scholar 

  161. Verlinden RA, Hill DJ, Kenward MA, Williams CD, Radecka I (2007) Bacterial synthesis of biodegradable polyhydroxyalkanoates. J Appl Microbiol 102:1437–1449

    CAS  PubMed  Article  Google Scholar 

  162. Vorholt JA (2012) Microbial life in the phyllosphere. Nat Rev Microbiol 10:828–840

    CAS  PubMed  Article  Google Scholar 

  163. Vorholt JA, Thauer RK (2002) Molybdenum and tungsten enzymes in C1 metabolism. Met Ions Biol Syst 39:571–619

    CAS  PubMed  Google Scholar 

  164. Vorholt JA, Chistoserdova L, Lidstrom ME, Thauer RK (1998) The NADP-dependent methylene tetrahydromethanopterin dehydrogenase in Methylobacterium extorquens AM1. J Bacteriol 180:5351–5356

    CAS  PubMed  PubMed Central  Google Scholar 

  165. Vorholt JA, Chistoserdova L, Stolyar SM, Thauer RK, Lidstrom ME (1999) Distribution of tetrahydromethanopterin-dependent enzymes in methylotrophic bacteria and phylogeny of methenyl tetrahydromethanopterin cyclohydrolases. J Bacteriol 181:5750–5757

    CAS  PubMed  PubMed Central  Google Scholar 

  166. Vorholt JA, Marx CJ, Lidstrom ME, Thauer RK (2000) Novel formaldehyde-activating enzyme in Methylobacterium extorquens AM1 required for growth on methanol. J Bacteriol 182:6645–6650

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  167. Vuilleumier S, Chistoserdova L, Lee MC, Bringel F, Lajus A, Zhou Y, Gourion B, Barbe V, Chang J, Cruveiller S, Dossat C, Gillett W, Gruffaz C, Haugen E, Hourcade E, Levy R, Mangenot S, Muller E, Nadalig T, Pagni M, Penny C, Peyraud R, Robinson DG, Roche D, Rouy Z, Saenampechek C, Salvignol G, Vallenet D, Wu Z, Marx CJ, Vorholt JA, Olson MV, Kaul R, Weissenbach J, Medigue C, Lidstrom ME (2009) Methylobacterium genome sequences: a reference blueprint to investigate microbial metabolism of C1 compounds from natural and industrial sources. PLoS One 4:e5584

    PubMed  PubMed Central  Article  CAS  Google Scholar 

  168. Wilson MC, Moore BS (2012) Beyond ethylmalonyl-CoA: the functional role of crotonyl-CoA carboxylase/reductase homologs in expanding polyketide diversity. Nat Prod Rep 29:72–86

    CAS  PubMed  Article  Google Scholar 

  169. Yang S, Hoggard JC, Lidstrom ME, Synovec RE (2013) Comprehensive discovery of 13C labeled metabolites in the bacterium Methylobacterium extorquens AM1 using gas chromatography–mass spectrometry. J Chromatogr A 1317:175–185

    CAS  PubMed  Article  Google Scholar 

  170. Zhang M, Lidstrom ME (2003) Promoters and transcripts for genes involved in methanol oxidation in Methylobacterium extorquens AM1. Microbiology 149:1033–1040

    CAS  PubMed  Article  Google Scholar 

  171. Zhang M, FitzGerald KA, Lidstrom ME (2005) Identification of an upstream regulatory sequence that mediates the transcription of mox genes in Methylobacterium extorquens AM1. Microbiology 151:3723–3728

    CAS  PubMed  Article  Google Scholar 

Download references

Acknowledgments

Work related to methylotrophy in the authors’ laboratories is supported by a grant from FP7 project “Promyse” and a grant from the Swiss SystemsX.ch initiative within the framework of the ERA-Net ERASysAPP, MetApp.

Author information

Affiliations

Authors

Corresponding author

Correspondence to Julia A. Vorholt.

Additional information

Andrea M. Ochsner and Frank Sonntag contributed equally to the manuscript.

Electronic supplementary material

Below is the link to the electronic supplementary material.

ESM 1

(PDF 666 kb)

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Ochsner, A.M., Sonntag, F., Buchhaupt, M. et al. Methylobacterium extorquens: methylotrophy and biotechnological applications. Appl Microbiol Biotechnol 99, 517–534 (2015). https://doi.org/10.1007/s00253-014-6240-3

Download citation

Keywords

  • Methylobacterium extorquens
  • Methanol
  • Methylotrophy
  • Industrial biotechnology