Skip to main content
Log in

l-Ribose isomerase and mannose-6-phosphate isomerase: properties and applications for l-ribose production

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

Abstract

l-Ribose is a synthetic l-form monosaccharide. It is a building block of many novel nucleotide analog anti-viral drugs. Bio-production of l-ribose relies on a two-step reaction: (i) conversion of l-arabinose to l-ribulose by the catalytic action of l-arabinose isomerase (l-AI) and (ii) conversion of l-ribulose to l-ribose by the catalytic action of l-ribose isomerase (l-RI, EC 5.3.1.B3) or mannose-6-phosphate isomerase (MPI, EC 5.3.1.8, alternately named as phosphomannose isomerase). Between the two enzymes, l-RI is a rare enzyme that was discovered in 1996 by Professor Izumori’s group, whereas MPI is an essential enzyme in metabolic pathways in humans and microorganisms. Recent studies have focused on their potentials for industrial production of l-ribose. This review summarizes the applications of l-RI and MPI for l-ribose production.

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.

Scheme 1
Fig. 1

Similar content being viewed by others

References

  • Ahmed Z, Shimonishi T, Bhuiyan SH, Utamura M, Takada G, Izumori K (1999) Biochemical preparation of L-ribose and L-arabinose from ribitol: a new approach. J Biosci Bioeng 88(4):444–448

    Article  CAS  PubMed  Google Scholar 

  • Beerens K, Desmet T, Soetaert W (2012) Enzymes for the biocatalytic production of rare sugars. J Ind Microbiol Biot 39(6):823–834

    Article  CAS  Google Scholar 

  • Bhosale SH, Rao MB, Deshpande VV (1996) Molecular and industrial aspects of glucose isomerase. Microbiol Rev 60(2):280–300

    CAS  PubMed  PubMed Central  Google Scholar 

  • Cho BH, Kim JH, Jeon HB, Kim KS (2005) A new efficient and practical synthesis of 2-deoxy-L-ribose. Tetrahedron 61(18):4341–4346

    Article  CAS  Google Scholar 

  • Chong Y, Chu CK (2002) Efficient synthesis of 2-deoxy-L-erythro-pentose (2-deoxy-L-ribose) from L-arabinose. Carbohyd Res 337(5):397–402

    Article  CAS  Google Scholar 

  • Cleasby A, Wonacott A, Skarzynski T, Hubbard RE, Davies GJ, Proudfoot AE, Bernard AR, Payton MA, Wells TN (1996) The X-ray crystal structure of phosphomannose isomerase from Candida albicans at 1.7 Å resolution. Nat Struct Mol Biol 3(5):470–479

    Article  CAS  Google Scholar 

  • Collins LV, Hackett J (1991) Sequence of the phosphomannose isomerase-encoding gene of Salmonella typhimurium. Gene 103(1):135–136

    Article  CAS  PubMed  Google Scholar 

  • Davenport RC, Bash PA, Seaton BA, Karplus M, Petsko GA, Ringe D (1991) Structure of the triosephosphate isomerase-phosphoglycolohydroxamate complex: an analog of the intermediate on the reaction pathway. Biochemistry 30(24):5821–5826

    Article  CAS  PubMed  Google Scholar 

  • De Muynck C, Pereira C, Soetaert W, Vandamme E (2006) Dehydrogenation of ribitol with Gluconobacter oxydans: production and stability of L-ribulose. J Biotechnol 125(3):408–415

    Article  CAS  PubMed  Google Scholar 

  • Englesberg E (1961) Enzymatic characterization of 17 L-arabinose negative mutants of Escherichia coli. J Bacteriol 81(6)

  • Gowda G, Sagurthi SR, Savithri HS, Murthy MRN (2008) Cloning, expression, purification, crystallization and preliminary X-ray crystallographic analysis of the mannose 6-phosphate isomerase from Salmonella typhimurium. Acta Crystallogr Sect F Struct Biol Cryst Commun 64(2):81–84

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Helanto M, Kiviharju K, Granström T, Leisola M, Nyyssölä A (2009) Biotechnological production of L-ribose from L-arabinose. Appl Microbiol Biotechnol 83(1):77–83

    Article  CAS  PubMed  Google Scholar 

  • Hu C, Li L, Zheng Y, Rui L, Hu C (2011) Perspectives of biotechnological production of L-ribose and its purification. Appl Microbiol Biotechnol 92(3):449–455

    Article  CAS  PubMed  Google Scholar 

  • Hung XG, Yu MY, Chen YC, Fang TY (2015) Characterization of a recombinant L-ribose isomerase from Geodermatophilus Obscurus DSM 43160 and application of this enzyme to the production of L-ribose from L-arabinose. J Mar Sci Tech Taiw 23(4):558–566

    Google Scholar 

  • Itoh H, Okaya H, Khan AR, Tajima S, Hayakawa S, Izumori K (1994) Purification and characterization of D-tagatose 3-epimerase from Pseudomonas sp. ST-24. Biosci Biotechnol Biochem 58(12):2168–2171

    Article  CAS  Google Scholar 

  • Jensen SO, Reeves PR (1998) Domain organisation in phosphomannose isomerases (types I and II). Biochim Biophys Acta Protein Struct Mol Enzymol 1382(1):5–7

    Article  CAS  Google Scholar 

  • Jung ME, Xu Y (1997) Efficient syntheses of L-ribose and 2-deoxy L-ribose from D-ribose and L-arabinose. Tetrahedron Lett 38(24):4199–4202

    Article  CAS  Google Scholar 

  • Juza M, Mazzotti M, Morbidelli M (2000) Simulated moving-bed chromatography and its application to chirotechnology. Trends Biotechnol 18(3):108–118

    Article  CAS  PubMed  Google Scholar 

  • Kawaguchi T, Hara M, Ueda M (2001) Process for producing L-ribose. EP1083234

  • Kim P (2004) Current studies on biological tagatose production using L-arabinose isomerase: a review and future perspective. Appl Microbiol Biotechnol 65(3):243–249

    CAS  PubMed  Google Scholar 

  • Kim HJ, Hyun EK, Kim YS, Lee YJ, DK O (2006) Characterization of an Agrobacterium tumefaciens D-psicose 3-epimerase that converts D-fructose to D-psicose. Appl Environ Microb 72(2):981–985

    Article  CAS  Google Scholar 

  • Kim KR, Seo ES, Oh DK (2014) L-Ribose production from L-arabinose by immobilized recombinant Escherichia coli co-expressing the L-arabinose isomerase and mannose-6-phosphate isomerase genes from Geobacillus thermodenitrificans. Appl Microbiol Biotechnol 172(1):275–288

    CAS  Google Scholar 

  • Lim YR, Yeom SJ, DK O (2012) Production of L-ribose from L-ribulose by a triple-site variant of mannose-6-phosphate isomerase from Geobacillus thermodenitrificans. Appl Environ Microb 78(11):3880–3884

    Article  CAS  Google Scholar 

  • Manjasetty BA, Chance MR (2006) Crystal structure of Escherichia coli L-arabinose isomerase (ECAI), the putative target of biological tagatose production. J Mol Biol 360(2):297–309

    Article  CAS  PubMed  Google Scholar 

  • Menavuvu BT, Poonperm W, Leang K, Noguchi N, Okada H, Morimoto K, Granström TB, Takada G, Izumori K (2006) Efficient biosynthesis of D-allose from D-psicose by cross-linked recombinant L-rhamnose isomerase: separation of product by ethanol crystallization. J Biosci Bioeng 101(4):340–345

    Article  CAS  PubMed  Google Scholar 

  • Miles JS, Guest JR (1984) Complete nucleotide sequence of the fumarase gene fumA, of Escherichia coli. Nucleic Acids Res 12(8):3631–3642

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Mizanur RM, Takata G, Izumori K (2001) Cloning and characterization of a novel gene encoding L-ribose isomerase from Acinetobacter sp. strain DL-28 in Escherichia coli. Biochim Biophys Acta (BBA) Gene Struct Expr 1521(1):141–145

    Article  CAS  Google Scholar 

  • Morimoto K, Terami Y, Maeda YI, Yoshihara A, Takata G, Izumori K (2013) Cloning and characterization of the L-ribose isomerase gene from Cellulomonas parahominis MB426. J Biosci Bioeng 115(4):377–381

    Article  CAS  PubMed  Google Scholar 

  • Mu W, Yu L, Zhang W, Zhang T, Jiang B (2015) Isomerases for biotransformation of D-hexoses. Appl Microbiol Biotechnol 99(16):6571–6584

    Article  CAS  PubMed  Google Scholar 

  • Oh DK (2007) Tagatose: properties, applications, and biotechnological processes. Appl Microbiol Biotechnol 76(1):1–8

    Article  CAS  PubMed  Google Scholar 

  • Okano K (2009) Synthesis and pharmaceutical application of L-ribose. Tetrahedron 65(10):1937–1949

    Article  CAS  Google Scholar 

  • Proudfoot AE, Turcatti G, Wells TN, Payton MA, Smith DJ (1994) Purification cDNA cloning and heterologous expression of human phosphomannose isomerase. Eur J Biochem 219(1–2):415–423

    Article  CAS  PubMed  Google Scholar 

  • Sagurthi SR, Gowda G, Savithri HS, Murthy MRN (2009) Structures of mannose-6-phosphate isomerase from Salmonella typhimurium bound to metal atoms and substrate: implications for catalytic mechanism. Acta Crystallogr Sec D Biol Crystallogr 65(7):724–732

    Article  CAS  Google Scholar 

  • Shimonishi T, Izumori K (1996) A new enzyme, L-ribose isomerase from Acinetobacter sp. strain DL-28. J Ferment Bioeng 81(6):493–497

    Article  CAS  Google Scholar 

  • Shin HC, Jang MU, Lee HG, Kim MJ, Park JM, Jang KI, Kim TJ (2013) Effect of temperature and pH on interconversion between fructose and mannose catalyzed by Thermotoga neapolitana mannose-6-phosphate isomerase. Food Sci Biotechnol 22(1):39–44

    Article  CAS  Google Scholar 

  • Sigdel S, Singh R, Kim TS, Li J, Kim SY, Kim IW, Jung WS, Pan CH, Kang YC, Lee JK (2015) Characterization of a mannose-6-phosphate isomerase from Bacillus amyloliquefaciens and its application in fructose-6-phosphate production. PLoS One 10(7):e0131585

    Article  PubMed  PubMed Central  Google Scholar 

  • Swan MK, Hansen T, Schönheit P, Davies C (2004) A novel phosphoglucose isomerase (PGI)/phosphomannose isomerase from the crenarchaeon Pyrobaculum aerophilum is a member of the PGI superfamily structural evidence at 1.16 Å resolution. J Biol Chem 279(38):39838–39845

    Article  CAS  PubMed  Google Scholar 

  • Terami Y, Yoshida H, Uechi K, Morimoto K, Takata G, Kamitori S (2015) Essentiality of tetramer formation of Cellulomonas parahominis L-ribose isomerase involved in novel L-ribose metabolic pathway. Appl Microbiol Biotechnol 99(15):6303–6313

    Article  CAS  PubMed  Google Scholar 

  • Tolley S, Davies G, Hubbard RE, Smith DJ, Proudfoot AE, Payton MA, Cleasby A, Wonacott A, Wells TN (1994) Crystallization and preliminary X-ray analysis of Candida albicans phosphomannose isomerase. J Mol Biol 237(3):349–350

    Article  CAS  PubMed  Google Scholar 

  • van Staalduinen LM, Park CS, Yeom SJ, Adams-Cioaba MA, Oh DK, Jia Z (2010) Structure-based annotation of a novel sugar isomerase from the pathogenic E. coli O157:H7. J Mol Biol 401(5):866–881

    Article  PubMed  Google Scholar 

  • Wells TN, Coulin F, Payton MA, Proudfoot AE (1993) Phosphomannose isomerase from Saccharomyces cerevisiae contains two inhibitory metal ion binding sites. Biochemistry 32(5):1294–1301

    Article  CAS  PubMed  Google Scholar 

  • Wells TN, Scully P, Magnenat E (1994) Arginine 304 is an active site residue in phosphomannose isomerase from Candida albicans. Biochemistry 33(19):5777–5782

    Article  CAS  PubMed  Google Scholar 

  • Whitlow M, Howard AJ, Finzel BC, Poulos TL, Winborne E, Gilliland GL (1991) A metal-mediated hydride shift mechanism for xylose isomerase based on the 1.6 Å Streptomycs rubiginosus structure with xylitol and D-xylose. Proteins Struct Function Bioinformatics 9(3):153–173

    Article  CAS  Google Scholar 

  • Xu Z, Li S, Feng X, Liang J, Xu H (2014) L-Arabinose isomerase and its use for biotechnological production of rare sugars. Appl Microbiol Biotechnol 98(21):8869–8878

    Article  CAS  PubMed  Google Scholar 

  • Xu H, Liu C, Xu Z, Wang X, Li S, Feng XH (2016a) An L-ribose isomerase and its application in bio-production of L-ribose. Chinese patent no. 201610218779.3

  • Xu Z, Wang R, Liu C, Chi B, Gao J, Chen B, Xu H (2016b) A new L-arabinose isomerase with copper ion tolerance is suitable for creating protein-inorganic hybrid nanoflowers with enhanced enzyme activity and stability. RSC Adv 6:30791–30794

    Article  CAS  Google Scholar 

  • Yeom SJ, Kim NH, Yoon RY, Kwon HJ, Park CS, Oh DK (2009a) Characterization of a mannose-6-phosphate isomerase from Geobacillus thermodenitrificans that converts monosaccharides. Biotechnol Lett 31(8):1273–1278

    Article  CAS  PubMed  Google Scholar 

  • Yeom SJ, Ji JH, Kim NH, Park CS, Oh DK (2009b) Substrate specificity of a mannose-6-phosphate isomerase from Bacillus subtilis and its application in the production of L-ribose. Appl Environ Microb 75(14):4705–4710

    Article  CAS  Google Scholar 

  • Yeom SJ, Kim NH, Park CS, Oh DK (2009c) L-Ribose production from L-arabinose by using purified L-arabinose isomerase and mannose-6-phosphate isomerase from Geobacillus thermodenitrificans. Appl Environ Microb 75(21):6941–6943

    Article  CAS  Google Scholar 

  • Yeom SJ, Kim YS, Lim YR, Jeong KW, Lee JY, Kim Y, Oh DK (2011a) Molecular characterization of a novel thermostable mannose-6-phosphate isomerase from Thermus thermophilus. Biochimie 93(10):1659–1667

    Article  CAS  PubMed  Google Scholar 

  • Yeom SJ, Seo ES, Kim BN, Kim YS, Oh DK (2011b) Characterization of a mannose-6-phosphate isomerase from Thermus thermophilus and increased L-ribose production by its R142N mutant. Appl Environ Microb 77(3):762–767

    Article  CAS  Google Scholar 

  • Yeom SJ, Kim YS, Oh DK (2013) Development of novel sugar isomerases by optimization of active sites in phosphosugar isomerases for monosaccharides. Appl Environ Microb 79(3):982–988

    Article  CAS  Google Scholar 

  • Yoshida H, Yoshihara A, Teraoka M, Terami Y, Takata G, Izumori K, Kamitori S (2014) X-ray structure of a novel L-ribose isomerase acting on a non-natural sugar L-ribose as its ideal substrate. FEBS J 281(14):3150–3164

    Article  CAS  PubMed  Google Scholar 

  • Zhang YW, Prabhu P, Lee JK (2009) Immobilization of Bacillus licheniformis L-arabinose isomerase for semi-continuous L-ribulose production. Biosci Biotech Biochem 73(10):2234–2239

    Article  CAS  Google Scholar 

  • Zhang YW, Prabhu P, Lee JK (2010a) Alginate immobilization of recombinant Escherichia coli whole cells harboring L-arabinose isomerase for L-ribulose production. Bioprocess Biosyst Eng 33(6):741–748

    Article  CAS  PubMed  Google Scholar 

  • Zhang YW, Jeya M, Lee JK (2010b) L-Ribulose production by an Escherichia coli harboring L-arabinose isomerase from Bacillus licheniformis. Appl Microbiol Biotechnol 87(6):1993–1999

    Article  CAS  PubMed  Google Scholar 

  • Zhang YW, Jeya M, Lee JK (2011) Enhanced activity and stability of L-arabinose isomerase by immobilization on aminopropyl glass. Appl Microbiol Biotechnol 89(5):1435–1442

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Hong Xu.

Ethics declarations

Ethical approval

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

Funding

We gratefully acknowledge the financial support from the National Natural Science Foundation of China (no. 31400053 to Z. Xu), the Natural Science Foundation of Jiangsu Province (no. BK20140933 to Z. Xu), the Jiangsu Province Science and Technology Support Plan Project (no. BE2015366 to H. Xu), the Science and Technology Program of Joint Innovation Fund—A Prospective Joint Research Project in Jiangsu Province (no. BY2014005-10 to J.F. Liang), and the State Key Laboratory of Materials-Oriented Chemical Engineering (no. KL15-09 to J. Zhou).

Conflict of interest

The authors declare that there is no conflict of interest.

Electronic supplementary material

ESM 1

(PDF 117 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Xu, Z., Sha, Y., Liu, C. et al. l-Ribose isomerase and mannose-6-phosphate isomerase: properties and applications for l-ribose production. Appl Microbiol Biotechnol 100, 9003–9011 (2016). https://doi.org/10.1007/s00253-016-7834-8

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00253-016-7834-8

Keywords

Navigation