Abstract
Carbohydrate epimerases and isomerases are essential for the metabolism and synthesis of carbohydrates. In this study, Runella slithyformis Runsl_4512 and Dyadobacter fermentans Dfer_5652 were characterized from a cluster of uncharacterized proteins of the acylglucosamine 2-epimerase (AGE) superfamily. These proteins catalyzed the intramolecular conversion of d-mannose to d-glucose, whereas they did not act on β-(1 → 4)-mannobiose, N-acetyl-d-glucosamine, and d-fructose, which are substrates of known AGE superfamily members. The kcat/Km values of Runsl_4512 and Dfer_5652 for d-mannose epimerization were 3.89 and 3.51 min−1 mM−1, respectively. Monitoring the Runsl_4512 reaction through 1H-NMR showed the formation of β-d-glucose and β-d-mannose from d-mannose and d-glucose, respectively. In the reaction with β-d-glucose, β-d-mannose was produced at the initial stage of the reaction, but not in the reaction with α-d-glucose. These results indicate that Runsl_4512 catalyzed the 2-epimerization of the β-anomer substrate with a net retention of the anomeric configuration. Since 2H was obviously detected at the 2-C position of d-mannose and d-glucose in the equilibrated reaction mixture produced by Runsl_4512 in 2H2O, this enzyme abstracts 2-H from the substrate and adds another proton to the intermediate. This mechanism is in accordance with the mechanism proposed for the reactions of other epimerases of the AGE superfamily, that is, AGE and cellobiose 2-epimerase. Upon reaction with 500 g/L d-glucose at 50 °C and pH 8.0, Runsl_4512 and Dfer_5652 produced d-mannose with a 24.4 and 22.8% yield, respectively. These d-mannose yields are higher than those of other enzyme systems, and ME acts as an efficient biocatalyst for producing d-mannose.
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References
Bhosale SH, Rao MB, Deshpande VV (1996) Molecular and industrial aspects of glucose isomerase. Microbiol Rev 60:280–300
Chen FE, Zhao JF, Xiong FJ, Xie B, Zhang P (2007) An improved synthesis of a key intermediate for (+)-biotin from d-mannose. Carbohydr Res 342:2461–2464. https://doi.org/10.1016/j.carres.2007.06.029
de Lonlay P, Seta N (2009) The clinical spectrum of phosphomannose isomerase deficiency, with an evaluation of mannose treatment for CDG-Ib. Biochim Biophys Acta 1792:841–843. https://doi.org/10.1016/j.bbadis.2008.11.012
Denger K, Weiss M, Felux AK, Schneider A, Mayer C, Spiteller D, Huhn T, Cook AM, Schleheck D (2014) Sulphoglycolysis in Escherichia coli K-12 closes a gap in the biogeochemical sulphur cycle. Nature 507:114–117. https://doi.org/10.1038/nature12947
Fujiwara T, Saburi W, Inoue S, Mori H, Matsui H, Tanaka I, Yao M (2013) Crystal structure of Ruminococcus albus cellobiose 2-epimerase: structural insights into epimerization of unmodified sugar. FEBS Lett 587:840–846. https://doi.org/10.1016/j.febslet.2013.02.007
Fujiwara T, Saburi W, Matsui H, Mori H, Yao M (2014) Structural insights into the epimerization of β-1,4-linked oligosaccharides catalyzed by cellobiose 2-epimerase, the sole enzyme epimerizing non-anomeric hydroxyl groups of unmodified sugars. J Biol Chem 289:3405–3415. https://doi.org/10.1074/jbc.M113.531251
Ghoreishi SM, Shahrestani RG (2009) Innovative strategies for engineering mannitol production. Trends Food Sci Technol 20:263–270. https://doi.org/10.1016/j.tifs.2009.03.006
Hirose J, Kinoshita Y, Fukuyama S, Hayashi S, Yokoi H, Takasaki Y (2003) Continuous isomerization of d-fructose to d-mannose by immobilized Agrobacterium radiobacter cells. Biotechnol Lett 25:349–352. https://doi.org/10.1023/A:1022301725817
Hu X, Zhang P, Miao M, Zhang T, Jiang B (2016) Development of a recombinant d-mannose isomerase and its characterizations for d-mannose synthesis. Int J Biol Macromol 89:328–335. https://doi.org/10.1016/j.ijbiomac.2016.04.083
Huang J, Yu L, Zhang W, Zhang T, Guang C, Mu W (2018) Production of d-mannose from d-glucose by co-expression of d-glucose isomerase and d-lyxose isomerase in Escherichia coli. J Sci Food Agric 98:4895–4902. https://doi.org/10.1002/jsfa.9021
Iida T, Hayashi N, Yamada T, Yoshikawa Y, Miyazato S, Kishimoto Y, Okuma K, Tokuda M, Izumori K (2010) Failure of d-psicose absorbed in the small intestine to metabolize into energy and its low large intestinal fermentability in humans. Metabolism 59:206–214. https://doi.org/10.1016/j.metabol.2009.07.018
Ito S, Taguchi H, Hamada S, Kawauchi S, Ito H, Senoura T, Watanabe J, Nishimukai M, Ito S, Matsui H (2008) Enzymatic properties of cellobiose 2-epimerase from Ruminococcus albus and the synthesis of rare oligosaccharides by the enzyme. Appl Microbiol Biotechnol 79:433–441. https://doi.org/10.1007/s00253-008-1449-7
Itoh T, Mikami B, Maru I, Ohta Y, Hashimoto W, Murata K (2000) Crystal structure of N-acyl-d-glucosamine 2-epimerase from porcine kidney at 2.0 Å resolution. J Mol Biol 303:733–744. https://doi.org/10.1006/jmbi.2000.4188
Itoh T, Mikami B, Hashimoto W, Murata K (2008) Crystal structure of YihS in complex with d-mannose: structural annotation of Escherichia coli and Salmonella enterica yihS-encoded proteins to an aldose-ketose isomerase. J Mol Biol 377:1443–1459. https://doi.org/10.1016/j.jmb.2008.01.090
Kasumi T, Mori S, Kaneko S, Matsumoto H, Kobayashi Y, Koyama Y (2014) Characterization of mannose isomerase from a cellulolytic actinobacteria Thermobifida fusca MBL10003. J Appl Glycosci 61:21–25. https://doi.org/10.5458/jag.jag.JAG-2013_008
Katoh K, Rozewicki J, Yamada KD (2017) MAFFT online service: multiple sequence alignment, interactive sequence choice and visualization. Brief Bioinform. https://doi.org/10.1093/bib/bbx108
Kawahara R, Saburi W, Odaka R, Taguchi H, Ito S, Mori H, Matsui H (2012) Metabolic mechanism of mannan in a ruminal bacterium, Ruminococcus albus, involving two mannoside phosphorylases and cellobiose 2-epimerase. Discovery of a new carbohydrate phosphorylase, β-1,4-mannooligosaccharide phosphorylase. J Biol Chem 287:42389–42399. https://doi.org/10.1074/jbc.M112.390336
Kiyohara M, Tachizawa A, Nishimoto M, Kitaoaka M, Ashida H, Yamamoto K (2009) Prebiotic effect of lacto-N-biose I on bifidobacterial growth. Biosci Biotechnol Biochem 73:1175–1179. https://doi.org/10.1271/bbb.80697
Kranjčec B, Papeš D, Altarac S (2014) d-mannose powder for prophylaxis of recurrent urinary tract infections in women: a randomized clinical trial. World J Urol 32:79–84. https://doi.org/10.1007/s00345-013-1091-6
Kuyper M, Winkler AA, van Dijken JP, Pronk JT (2004) Minimal metabolic engineering of Saccharomyces cerevisiae for efficient anaerobic xylose fermentation: a proof of principle. FEMS Yeast Res 4:655–664. https://doi.org/10.1016/j.femsyr.2004.01.003
Lee YC, Wu HM, Chang YN, Wang WC, Hsu WH (2007) The central cavity from the (alpha/alpha)6 barrel structure of Anabaena sp. CH1 N-acetyl-d-glucosamine 2-epimerase contains two key histidine residues for reversible conversion. J Mol Biol 367:895–908. https://doi.org/10.1016/j.jmb.2006.11.001
Murakami Y, Ojima-Kato T, Saburi W, Mori H, Matsui H, Tanabe S, Suzuki T (2015) Supplemental epilactose prevents metabolic disorders through uncoupling protein-1 induction in the skeletal muscle of mice fed high-fat diets. Br J Nutr 114:1774–1783. https://doi.org/10.1017/S0007114515003505
Nishimoto M, Kitaoka M (2007) Practical preparation of lacto-N-biose I, a candidate for the bifidus factor in human milk. Biosci Biotechnol Biochem 71:2101–2104. https://doi.org/10.1271/bbb.70320
Nishimukai M, Watanabe J, Taguchi H, Senoura T, Hamada S, Matsui H, Yamamoto T, Wasaki J, Hara H, Ito S (2008) Effects of epilactose on calcium absorption and serum lipid metabolism in rats. J Agric Food Chem 56:10340–10345. https://doi.org/10.1021/jf801556m
Ochiai M, Nakanishi Y, Yamada T, Iida T, Matsuo T (2013) Inhibition by dietary d-psicose of body fat accumulation in adult rats fed a high-sucrose diet. Biosci Biotechnol Biochem 77:1123–1126. https://doi.org/10.1271/bbb.130019
Ochiai M, Onishi K, Yamada T, Iida T, Matsuo T (2014) d-Psicose increases energy expenditure and decreases body fat accumulation in rats fed a high-sucrose diet. Int J Food Sci Nutr 65:245–250. https://doi.org/10.3109/09637486.2013.845653
Oyofo BA, DeLoach JR, Corrier DE, Norman JO, Ziprin RL, Mollenhauer HH (1989) Prevention of Salmonella typhimurium colonization of broilers with D-mannose. Poult Sci 68:1357–1360. https://doi.org/10.3382/ps.0681357
Park CS, Kwon HJ, Yeom SJ, Oh DK (2010a) Mannose production from fructose by free and immobilized d-lyxose isomerases from Providencia stuartii. Biotechnol Lett 32:1305–1309. https://doi.org/10.1007/s10529-010-0300-2
Park CS, Yeom SJ, Lim YR, Kim YS, Oh DK (2010b) Characterization of a recombinant thermostable l-rhamnose isomerase from Thermotoga maritima ATCC 43589 and its application in the production of l-lyxose and l-mannose. Biotechnol Lett 32:1947–1953. https://doi.org/10.1007/s10529-010-0385-7
Park CS, Kim JE, Choi JG, Oh DK (2011) Characterization of a recombinant cellobiose 2-epimerase from Caldicellulosiruptor saccharolyticus and its application in the production of mannose from glucose. Appl Microbiol Biotechnol 92:1187–1196. https://doi.org/10.1007/s00253-011-3403-3
Ranta K, Nieminen K, Ekholm FS, Poláková M, Roslund MU, Saloranta T, Leino R, Savolainen J (2012) Evaluation of immunostimulatory activities of synthetic mannose- containing structures mimicking the β-(1→2)-linked cell wall mannans of Candida albicans. Clin Vaccine Immunol 19:1889–1893. https://doi.org/10.1128/CVI.00298-12
Saburi W (2016) Functions, structures, and applications of cellobiose 2-epimerase and glycoside hydrolase family 130 mannoside phosphorylases. Biosci Biotechnol Biochem 80:1294–1305. https://doi.org/10.1080/09168451.2016.1166934
Saburi W, Yamamoto T, Taguchi H, Hamada S, Matsui H (2010) Practical preparation of epilactose produced with cellobiose 2-epimerase from Ruminococcus albus NE1. Biosci Biotechnol Biochem 74:1736–1737. https://doi.org/10.1271/bbb.100353
Saburi W, Tanaka Y, Muto H, Inoue S, Odaka R, Nishimoto M, Kitaoka M, Mori H (2015) Functional reassignment of Cellvibrio vulgaris EpiA to cellobiose 2-epimerase and an evaluation of the biochemical functions of the 4-O-β-d-mannosyl-d-glucose phosphorylase-like protein, UnkA. Biosci Biotechnol Biochem 79:969–977. https://doi.org/10.1080/09168451.2015.1012146
Saburi W, Jaito N, Kato K, Tanaka Y, Yao M, Mori H (2018) Biochemical and structural characterization of Marinomonas mediterranea d-mannose isomerase Marme_2490 phylogenetically distant from known enzymes. Biochimie 144:63–73. https://doi.org/10.1016/j.biochi.2017.10.016
Schägger H, Cramer WA, von Jagow G (1994) Analysis of molecular masses and oligomeric states of protein complexes by blue native electrophoresis and isolation of membrane protein complexes by two-dimensional native electrophoresis. Anal Biochem 217:220–230. https://doi.org/10.1006/abio.1994.1112
Standley DM, Toh H, Nakamura H (2007) ASH structure alignment package: sensitivity and selectivity in domain classification. BMC Bioinformatics 8:116. https://doi.org/10.1186/1471-2105-8-116
Suzuki T, Nishimukai M, Shinoki A, Taguchi H, Fukiya S, Yokota A, Saburi W, Yamamoto T, Hara H, Matsui H (2010a) Ingestion of epilactose, a non-digestible disaccharide, improves postgastrectomy osteopenia and anemia in rats through the promotion of intestinal calcium and iron absorption. J Agric Food Chem 58:10787–10792. https://doi.org/10.1021/jf102563y
Suzuki T, Nishimukai M, Takechi M, Taguchi H, Hamada S, Yokota A, Ito S, Hara H, Matsui H (2010b) The nondigestible disaccharide epilactose increases paracellular Ca absorption via rho-associated kinase- and myosin light chain kinase-dependent mechanisms in rat small intestines. J Agric Food Chem 58:1927–1932. https://doi.org/10.1021/jf9035063
Takeshita K, Suga A, Takada G, Izumori K (2000) Mass production of d-psicose from d-fructose by a continuous bioreactor system using immobilized d-tagatose 3-epimerase. J Biosci Bioeng 90:453–455. https://doi.org/10.1016/S1389-1723(01)80018-9
Watanabe J, Nishimukai M, Taguchi H, Senoura T, Hamada S, Matsui H, Yamamoto T, Wasaki J, Hara H, Ito S (2008) Prebiotic properties of epilactose. J Dairy Sci 91:4518–4526. https://doi.org/10.3168/jds.2008-1367
Acknowledgments
We thank Dr. Eri Fukushi of the GC-MS & NMR Laboratory, Research Faculty of Agriculture, Hokkaido University for NMR data analysis; Mr. Yusuke Takada of the DNA sequencing facility of the Research Faculty of Agriculture, Hokkaido University for assistance with DNA sequence analysis; and Ms. Nozomi Takeda of the Global Facility Center, Hokkaido University for the amino acid analysis. We would like to thank Editage (www.editage.jp) for English language editing.
Funding
This work was supported in part by a Grant-in-Aid for Scientific Research (C) from the Ministry of Education, Culture, Sports, Science, and Technology of Japan [grant number 18K05382].
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Saburi, W., Sato, S., Hashiguchi, S. et al. Enzymatic characteristics of d-mannose 2-epimerase, a new member of the acylglucosamine 2-epimerase superfamily. Appl Microbiol Biotechnol 103, 6559–6570 (2019). https://doi.org/10.1007/s00253-019-09944-3
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DOI: https://doi.org/10.1007/s00253-019-09944-3