Skip to main content
Log in

Bifunctional xylanases and their potential use in biotechnology

  • Review
  • Published:
Journal of Industrial Microbiology & Biotechnology

Abstract

Plant cell walls are comprised of cellulose, hemicellulose and other polymers that are intertwined. This complex structure acts as a barrier to degradation by single enzyme. Thus, a cocktail consisting of bi and multifunctional xylanases and xylan debranching enzymes is most desired combination for the efficient utilization of these complex materials. Xylanases have prospective applications in the food, animal feed, and paper and pulp industries. Furthermore, in order to enhance feed nutrient digestibility and to improve wheat flour quality xylanase along with other glycohydrolases are often used. For these applications, a bifunctional enzyme is undoubtedly much more valuable as compared to monofunctional enzyme. The natural diversity of enzymes provides some candidates with evolved bifunctional activity. Nevertheless most resulted from the in vitro fusion of individual enzymes. Here we present bifunctional xylanases, their evolution, occurrence, molecular biology and potential uses in 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

  1. An JM, Kim YK, Lim WJ, Hong SY, An CL, Shin EC, Cho KM, Choi BR, Kang JM, Lee SM, Kim H, Yun HD (2005) Evaluation of a novel bifunctional xylanasecellulase constructed by gene fusion. Enzyme Microb Technol 36:989–995

    Article  CAS  Google Scholar 

  2. Annison G (1992) Commercial enzyme supplementation of wheat-based diets raises ileal glycanase activities and improves apparent metabolisable energy, starch and pentosan digestibilities in broiler chickens. Anim feed sci technol 38:105–121

    Article  CAS  Google Scholar 

  3. Arai R, Ueda H, Kitayama A, Kamiya N, Nagamune T, (2001) Design of the linkers which effectively separate domains of a bifunctional fusion protein. Protein Eng 14:529–532

    Article  CAS  Google Scholar 

  4. Balbas P (2001) Understanding the art of producing protein and nonprotein molecules in Escherichia coli. Mol Biotechnol 19:251–267

    Article  CAS  Google Scholar 

  5. Bayer EA (1998) Cellulose, cellulases, and cellulosomes. Curr Opin Struct Biol 8:548–557

    Article  CAS  Google Scholar 

  6. Bedford MR, Classen HL (1993) An in vitro assay for prediction of broiler intestinal viscosity and growth when fed rye-based diets in the presence of exogenous enzymes. Poult Sci 72:137–143

    CAS  Google Scholar 

  7. Beer MU, Wood PJ, Weisz J (1997) Molecular weight distribution and (1→3)(1→4)-β-d-glucan content of consecutive extracts of various oat and barley cultivars. Cereal Chem 74:476–480

    Article  CAS  Google Scholar 

  8. Bonnin E, Le Goff A, Saulnier L, Chaurand M, Thibault JF (1998) Preliminary characterisation of endogenous wheat arabinoxylan-degrading enzymic extracts. J Cereal Sci 28:53–62

    Article  CAS  Google Scholar 

  9. Bulock KG, Beardsley GP, Anderson KS (2002) The kinetic mechanism of the human bifunctional enzyme atic (5-amino-4-imidazolecarboxamide ribonucleotide transformylase/inosine 5′-monophosphate cyclohydrolase). J Biol Chem 277:22168–22174

    Article  CAS  Google Scholar 

  10. Bülow L, Mosbach K (1991) Multienzyme systems obtained by gene fusion. Trends Biotechnol 9: 226–231

    Article  Google Scholar 

  11. Bülow L, Mosbach K (1996) Fusion proteins:expression and function. Ann NY Acad Sci 99:376–382

    Article  Google Scholar 

  12. Bülow L, Carlsson H, Ljungcrantz P, Persson M, Lindbladh C (1996) Togetherness between proteins generated by gene fusion. Adv Mol Cell Biol 15A:297–310

    Google Scholar 

  13. Carpenter EP, Hawkins AR, Frost JW, Brown KA (1998) Structure of dehydroquinate synthase reveals an active site capable of multistep catalysis. Nature 394:299–301

    Article  CAS  Google Scholar 

  14. Cepeljnik T, Rincon MT, Flint HJ, Logar R (2006) Xyn11A, a multidomain multicatalytic enzyme from Pseudobutyrivibrio xylanivorans Mz5T. Folia Microbiol 51:263–267

    CAS  Google Scholar 

  15. Chen H, Yan X, Liu X, Wang M, Huang H, Jia X, Wang J (2006) Purification and characterization of novel bifunctional xylanase, XynIII, isolated from Aspergillus niger A-25. J Microbiol Biotechnol 16:1132–1138

    CAS  Google Scholar 

  16. Cherry JR, Lamsa MH, Schneider P, Vind J, Svendsen A, Jones A, Pedersen AH (1999) Directed evolution of a fungal peroxidase. Nat Biotechnol 17:333–334

    Article  Google Scholar 

  17. Collins T, Gerday C, Feller G (2005) Xylanases, xylanase families and extremophilic xylanases. FEMS Microbiol Rev 29:3–23

    Article  CAS  Google Scholar 

  18. Coughlan MP, Ljungdahl LG (1988) Comparative biochemistry of fungal and bacterial cellulolytic enzyme system. In: Aubert JP, Beguin P, Millet J (eds) Biochemistry and genetics of cellulose degradation. Academic Press, London, pp 11–30

    Google Scholar 

  19. Cui W, Wood PJ, Blackwell B, Nikiforuk J (2000) Physicochemical properties and structural characterization by two-dimensional NMR spectroscopy of wheat β-d-glucan-comparison with other cereal β-d-glucans. Carbo Poly 41:249–258

    Article  CAS  Google Scholar 

  20. Dattwyler RJ, Gomes-Solecki MJC, Luft BJ, Dunn J (2007) Method for developing chimeric, or “combination,” proteins that may advance the development of vaccines and diagnostic tests for Lyme disease. US. Patent 7,179,448

  21. Doi N, Yanagawa H (1999) Insertional gene fusion technology. FEBS Lett 457:1–4

    Article  CAS  Google Scholar 

  22. Emmanuel G, Desvaux M, Petitdemanage H (2002) Improvement of cellulolytic properties of Clostridium cellulolyticum by metabolic engineering. Appl Environ Microbiol 68:53–58

    Article  CAS  Google Scholar 

  23. Flint HJ, Martin J, McPherson CA, Daniel AS, Zhang JX (1993) A bifunctional enzyme with separate xylanase and β-(1,3-1,4)-glucanase domains, encoded by the XynD gene of Ruminococcus flavefaciens. J Bacteriol 175:2943–2951

    CAS  Google Scholar 

  24. Fooks L, Gibson G (2002) In vitro investigations of the effect of probiotics and prebiotics on selected human intestinal pathogens. FEMS Microbial Ecol 39:67–75

    Article  CAS  Google Scholar 

  25. Fuller JJ, Ross RJ, Dramm JR (1995) Nondestructive evaluation of honeycomb and surface checks in red oak lumber. Forest Prod J 45:42–44

    Google Scholar 

  26. George RA, Heringa J (2002) An analysis of protein domain linkers: their classification and role in protein folding. Protein Eng 15:871–879

    Article  CAS  Google Scholar 

  27. Gilbert F, Galgani F, Cadiou Y (1992) Rapid assessment of metabolic activity in marine microalgae: application in ecotoxicological tests and evaluation of water quality. Mar Biol 112:199–205

    Article  CAS  Google Scholar 

  28. Gokhale R, Khosla C (2000) Role of linkers in communication between protein modules. Curr Opin Chem Biol 4:22–27

    Article  CAS  Google Scholar 

  29. Gosalbes MJ, Perez-Gonzalez JA, Gonzalez R, Navarro A (1991) Two 3-glycanase genes are clustered in Bacillus polymyxa: molecular cloning, expression, and sequence analysis of genes encoding a xylanase and an endo-r-(1,3)-(1,4)-glucanase. J Bacteriol 173:7705–7710

    CAS  Google Scholar 

  30. Haros M, Rosell CM, Benedito C (2002) Improvement of flour quality through carbohydrases treatment during wheat tempering. J Agric Food Chem 50:4126–4130

    Article  CAS  Google Scholar 

  31. Helen C, Sarah L, Leif B (1996) Physical and kinetic effects on introduction of various linker regions in galactosidase/galactose dehydrogenase fusion enzymes. Biochim Biophys Acta 1293:154–160

    Google Scholar 

  32. Hernandez M, Hernandez-Coronado MJC, Montiel MD, Rodriguez J, Arias ME, (2001) Analysis of alkali-lignin in a paper mill effluent decolourised with two Streptomyces strains by gas chromatography-mass spectrometry after cupric oxide degradation. J Chromatography 919:389–394

    Article  CAS  Google Scholar 

  33. Hong SY, Lee JS, Cho KM, Math RK, Kim YH, Hong SJ, Cho YU, Kim H, Yun HD (2006) Assembling a novel bifunctional cellulase–xylanase from Thermotoga maritima by end-to-end fusion. Biotechnol Lett 28:1857–1862

    Article  CAS  Google Scholar 

  34. Huang X, Holden HM, Raushel FM (2001) Channeling of substrates and intermediates in enzyme-catalyzed reactions. Annu Rev Biochem 70:149–180

    Article  CAS  Google Scholar 

  35. Ingram LO, Eddy CK, Mackenzie KF, Conway T, Alterthum F (1989) Genetics of Zymomonas mobilis and ethanol production. Dev Ind Microbiol 30:53–69

    CAS  Google Scholar 

  36. Imaizumi K, Nakatsu Y, Sato M, Sedarnawati Y, Sugano M (1991) Effects of xylooligosaccharides on blood glucose, serum and liver lipids and cecum short-chain fatty acids in diabetic rats. Agric Biol Chem 55:199–205

    CAS  Google Scholar 

  37. Izumi Y, Kojo A (2003) Long-chain xylooligosaccharide compositions with intestinal function-improving and hypolipemic activities, and their manufacture. JP Patent 2003048901

  38. Jagusztynkrynicka EK, Clarkcurtiss JE, Curtiss R (1993) Escherichia coli heat-labile toxin subunit B fusions with Streptococcus sobrinus antigens expressed by Salmonella typhimurium oral vaccine strains: importance of the linker for antigenicity and biological activities of the hybrid proteins. Infect Immun 61:1004–15

    CAS  Google Scholar 

  39. James CL, Viola RE (2002) Production and characterization of bifunctional enzymes. Domain swapping to produce new bifunctional enzymes in the aspartate pathway. Biochem 41:3720–3725

    Article  CAS  Google Scholar 

  40. Jung H, Wilson DB, Walker LP (2002) Binding of Thermobifida fusca CDcel5A CDcel6B and CDcel48A to easily hydrolysable and recalcitrant cellulose fractions on BMCC. Enzyme Microb Technol 31:941–8

    Article  CAS  Google Scholar 

  41. Kazumitsu S, Boseki I, Norio S, Yoshimasa O (1987) Production of food and drink Japanese Patent JP 62278961

  42. Kazumitsu S, Boseki I, Norio S, Yoshimasa O (1997) Production of food and drink’, Japanese Patent JP 9248153

  43. Lamed R, Bayer EA (1988) The cellulosome concept: Exocellular enzyme reactor centers for efficient binding and cellulolysis. In: Aubert JP, Beguin P, Millet J (eds) Biochemistry and genetics of cellulose degradation. Academic Press, London, pp 101–116

    Google Scholar 

  44. Lemos MA, Teixeira JA, Domingues MRM, Mota M, Gama FM (2003) The enhancement of the celluloytic activity of cellobiohydrolase I and endoglucanase by the addition of cellulose binding domains derived from Trichoderma reesei. Enzyme Microb Technol 32:35–40

    Article  CAS  Google Scholar 

  45. Levy I, Paldi T, Shoseyov O (2003) Engineering a bifunctional starchcellulase cross-bridge protein. Biomaterials 25:1841–1849

    Article  CAS  Google Scholar 

  46. Liang PH, Anderson KS (1998) Substrate channeling and domain–domain interactions in bifunctional thymidylate synthase–dihydrofolate reductase. Biochem 37:12195–12205

    Article  CAS  Google Scholar 

  47. Lin LL, Thomson JA (1991) An analysis of the extracellular xylanases and cellulases of Butyrivibrio fibrisolvens H17c. FEMS Microbiol Lett 84:197–204

    Article  CAS  Google Scholar 

  48. Liu JH, Selinger LB, Hu YJ, Moloney MM, Cheng KJ, Beauchemin KA (1997) “An endoglucanase from the anaerobic fungus Orpinomyces joyonii: characterization of the gene and its product”. Can J Microbiol 43:477–485

    Article  CAS  Google Scholar 

  49. Longland AC, Theodorou MK, Sanderson R, Lister SJ, Powell CJ, Morris P (1995) Non-starch polysaccharide composition and in vitro fermentability of tropical forage legumes varying in phenolic content. Anim Feed Sci Technol 55:161–177

    Article  CAS  Google Scholar 

  50. Lu P, Feng M, Li2 W, Hu C (2006) Construction and characterization of a bifunctional fusion enzyme of Bacillus-sourced β-glucanase and xylanase expressed in Escherichia coli. FEMS Microbiol Lett 261:224–230

    Google Scholar 

  51. Makrides S C (1996) Strategies for achieving high-level expression of genes in Escherichia coli. Microbiol Rev 60:512–538

    CAS  Google Scholar 

  52. Malherbe S, Cloete TE (2003) Lignocellulose biodegradation: fundamentals and applitions. Environ Sci Biotechnol 30:425–444

    Google Scholar 

  53. Mathlouthi N, Lalles JP, Lepercq P, Juste C, Larbier M (2002) Xylanase and beta-glucanase supplementation improve conjugated bile acid fraction in intestinal contents and increase villus size of small intestine wall in broiler chickens fed a rye-based diet. J Anim Sci 80:2773–2779

    CAS  Google Scholar 

  54. Mathlouthi N, Juin H, Larbier M (2003) Effect of xylanase and beta-glucanase supplementation of wheat- or wheat- and barley-based diets on the performance of male turkeys. Br Poult Sci 44:291–298

    Article  CAS  Google Scholar 

  55. Meek TD, Garvey EP, Santi DV (1985) Meek TD, Garvey EP, Santi DV (1985) Purification and Characterization of the Bifunctional Thymidylate Synthetase-Dihydrofolate Reductase from Methotrexate-Resistant Leishmania tropica. Biochem 24:678–686

    Article  CAS  Google Scholar 

  56. Meng X, Slominski BA, Nyachoti CM, Campbell LD, Guenter W (2005) Degradation of cell wall polysaccharides by combinations of carbohydrase enzymes and their effect on nutrient utilization and broiler chicken performance. Poult Sci 84:37–47

    CAS  Google Scholar 

  57. Mesta L, Rascle D, Durand R, Revre M (2001) Construction of a chimeric xylanase using multidomain enzymes from Neocalllimastix frontalis. Enzyme Microb Technol 29:456–63

    Article  CAS  Google Scholar 

  58. Miles EW, Rhee S, Davies DR (1999) The molecular basis of substrate channelling. J Biol Chem 274:12193–12196

    Article  CAS  Google Scholar 

  59. Modler HW (1994) Bifidogenic factors—sources, metabolism and applications. Int Dairy J 4:383–407

    Article  Google Scholar 

  60. Morohoshi N (1991) Chemical characterization of wood and its components. In: Shiraishi N (eds) Wood cellulosic chemistry, Marcel Dekker, New York, pp 331–392

    Google Scholar 

  61. Murashima K, Kosugi A, Doi RH (2003) Synergistic Effects of cellulosomal xylanase and cellulases from Clostridium cellulovorans on plant cell wall degradation. J Bacteriol 185:1518–1524

    Article  CAS  Google Scholar 

  62. Nagradova N (2003) Interdomain communications in bifunctional enzymes: how are different activities coordinated? IUBMB Life 55:459–466

    Article  CAS  Google Scholar 

  63. Ni N, Jiang XN, Cai GP, Yang SF (1996) A novel bifunctional fusion enzyme catalyzing ethylene synthsis via 1-aminocyclopropane-1-carboxylic acid. J Biol Chem 271:25738–25741

    Article  Google Scholar 

  64. Nixon AE, Ostermeier M, Benkovic SJ (1998) Hybrid enzymes: manipulating enzyme design. Trends Biotechnol 16:258–264

    Article  CAS  Google Scholar 

  65. Numan MTh, Bhosle NB (2006) α-l-arabinofuranosidases: the potential applications in biotechnology. J Ind Microbiol Biotechnol 33:247–260

    Article  CAS  Google Scholar 

  66. Okar DA, Manzano NA, Navarro-Sabat A, Riera LS, Bartons R, Lange AJ (2001) PFK-2/FBPase-2: maker and breaker of the essential biofactor fructose-2,6-bisphosphate. Trends Biochem Sci 26:30–35

    Article  CAS  Google Scholar 

  67. Olsen LS, Nielson LR, Nexø BA, Wasserman K (1996) Somatic mutation detection in human biomonitoring. Pharmacol Toxicol 78:364–373

    Article  CAS  Google Scholar 

  68. Omogbenigun FO, Nyachoti CM, Slominski BA (2004) Dietary supplementation with multienzyme preparations improves nutrient utilization and growth performance in weaned pigs. J Anim Sci 82:1053–1061

    CAS  Google Scholar 

  69. Peters RJ, Ravn MM, Coates RM, Croteau RB (2001) Bifunctional abietadiene synthase: free diffusive transfer of the (+)-copalyl diphosphate intermediate between two distinct active sites. J Am Chem Soc 123:8974–8978

    Article  CAS  Google Scholar 

  70. Planas A (2000) Bacterial 1,3-1,4-β-glucanases: structure, function, and protein engineering. Biochim Biophys Acta 1543:361–382

    CAS  Google Scholar 

  71. Pohlschroder M, Leschine SB, Parola EC (1994) Multicomplex cellulase–xylanase system of Clostridium papyrosolvens C7. J Bacteriol 176:70–76

    CAS  Google Scholar 

  72. Rycroft CE, Jones MR, Gibson GR, Rasta RA (2001) A comparative in vitro evaluation of the fermentation properties of prebiotic oligosaccharides. J Appl Microbiol 91:878–887

    Article  CAS  Google Scholar 

  73. Salim ME, Classen HL, Campbell GL (1991) Response of chickens fed on hull-less barley to dietary β-glucanase at different ages. Anim feed sci technol 33:139–149

    Article  Google Scholar 

  74. Salobir J (1998) Effect of xylanase alone and in combination with β-glucanase on energy utilisation, nutrient utilization and intestinal viscosity of broilers fed diets based on two wheat samples. Arch Geflugelkd 5:209–213

    Google Scholar 

  75. Senn T, Pieper HJ (2001) The biotechnology of ethanol. In: Roehr (ed) Classical and future applications, vol 48. Wiley-VCH, Germany, pp 8–174

    Google Scholar 

  76. Seo M, Peeters AJM, Koiwai H, Oritani T, Marion-Poll A, Zeevaart JAD, Koornneef M, Kamiya Y, Koshiba T (2000) The Arabidopsis aldehyde oxidase 3 (AA03) gene product catalyzes the final step in abscisic acid biosynthesis in leaves. Proc Natl Acad Sci USA 97:12908–12913

    Article  CAS  Google Scholar 

  77. Sjöström E (1989) Wood chemistry: fundamentals and applications. Solar energy conversion—biomass production & conversion: wood chemistry, wood uses, anatomy, carbohydrates, cellulose, lignin, molecular structure. Academic Press, New York, p:235

    Google Scholar 

  78. Smith S (1994) The animal fatty acid synthase: one gene, one polypeptide, seven enzymes. J FASEB 8:1248–1259

    CAS  Google Scholar 

  79. Taeko I, Koichi N, Yasushi N, Akira K, Yoshinobu K (1998) ‘Food and drink effective in anti-obesity’, Japanese Patent JP 10290681

  80. Toivari MH, Aristidou A, Ruohonen L, Penttila M (2001) Conversion of xylose to ethanol by recombinant Saccharomyces cerevisiae: importance of xylulokinase (XKS1) and oxygen availability. Met Eng 3:236–249

    Article  CAS  Google Scholar 

  81. Toshio I, Noriyoshi I, Toshiaki K, Toshiyuki N, Kunimasa K (1990). ‘Production of Xylobiose’, Japanese Patent JP 2119790

  82. Tsuji N, Suzuki K, Kasuga-Aoki H, Matsumoto Y, Arakawa T, Isobe T (2001) Intranasal immunization with recombinant Ascaris suum 14-kDa antigen coupled with cholera toxin B subunit induces protective immunity to Ascaris suum infection in mice. Infect Immun 69:7285–7292

    Article  CAS  Google Scholar 

  83. Vázquez MJ, Alonso JL, Domínguez H, Parajó JC (2001) Xylooligosaccharides: manufacture and applications. Trends Food Sci Technol 11:387–393

    Article  Google Scholar 

  84. Vrzheshch PV (2007) Steadystate kinetics of bifunctional enzymes.Taking into account kinetic hierarchy of fast and slow catalytic cycles in a generalized model. Biochem (mosc) 72:936–43

    Article  CAS  Google Scholar 

  85. Wang B, Cheng B, Feng H (2008) Enriched arabinoxylan in corn fiber for value-added Products. Biotechnol Lett 30:275–279

    Article  CAS  Google Scholar 

  86. Warren RA, Gerhard JB, Gilkes NR, Owolabi JB, Kilburn DG, Miller RC (1987) A bifunctional exoglucanase–endoglucanase fusion protein. Gene 61:421–427

    Article  CAS  Google Scholar 

  87. Whitehead TR, Cotta MA (2001) Identification of a broad-specificity xylosidase/arabinosidase important for xylooligosaccharide fermentation by the ruminal anaerobe Selenomonas ruminantium GA192. Curr Microbial 43:293–298

    Article  CAS  Google Scholar 

  88. Wiselogel ST, Johnson D (1996) Biomass feedstock resources and composition In: Wyman CE (ed) Handbook on bioethanol: production and utilization (applied energy technology series). Taylor & Francis, London pp 105–118

    Google Scholar 

  89. Wong KK, Tan LU, Saddler JN (1988) Multiplicity of β-1,4-xylanase in microorganisms: functions and applications. Microbiol Rev 52:305–317

    CAS  Google Scholar 

  90. Xie G, Bruce DC, Challacombe JF, Chertkov O, Detter JC, Gilna P, Han CS, Lucas S, Misra M, Myers GL, Richardson P, Tapia R, Thayer N, Thompson LS, Brettin TS, Henrissat B, Wilson DB, McBride MJ (2007) Genome Sequence of the Cellulolytic Gliding Bacterium Cytophaga hutchinsonii. Appl Environ Microbiol 73:3536–3546

    Article  CAS  Google Scholar 

  91. Xue GP, Kari SG, Orpin CG (1992) A novel polysaccharide hydrolase cDNA (celD) from Neocallimastix patriciarum encoding three multi-functional catalytic domains with high endoglucanase, cellobiohydrolase and xylanase activities. J Gen Microbiol 138:2397–2403

    CAS  Google Scholar 

  92. Yourno J, Kohno T, Roth JR (1970) Enzyme evolution: Generation of a bifunctional enzyme by fusion of adjacent genes. Nat 228:820–825

    Article  CAS  Google Scholar 

  93. Yu P, McKinnon JJ, Christensen DA (2005) Improving the nutritional value of oat hulls for ruminant animals with pretreatment of a multienzyme cocktail: in vitro studies. J Anim Sci 83:1133–1141

    CAS  Google Scholar 

  94. Zhang JX, Flint HJ (1992) A bifunctional xylanase encoded by the XynA gene of the rumen cellulolytic bacterium Ruminococcus flavefaciens 17 comprises two dissimilar domains linked by an asparagine/glutamine-rich sequence. Mol Microbiol 6:1013–1023

    Article  CAS  Google Scholar 

Download references

Acknowledgments

We thank Dr S R Shetye, Director of the institute for encouragement and facilities. First author thank the Council of Scientific and Industrial Research, New Delhi for awarding her the Research Associate Fellowship and for providing partial financial support to carry out this work. We also appreciate the help given by all the staff members of the MCMRD. This is NIO contribution number 4352

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Rakhee Khandeparker.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Khandeparker, R., Numan, M.T. Bifunctional xylanases and their potential use in biotechnology. J Ind Microbiol Biotechnol 35, 635–644 (2008). https://doi.org/10.1007/s10295-008-0342-9

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10295-008-0342-9

Keywords

Navigation