Abstract
Diverse flavonoid glycosides are present in the plant kingdom. Advanced technologies have been utilized to synthesize glycosyl flavonoids which exhibit good physicochemical characteristics. Previously, novel isoquercitrin (IQ) mono-, di-, and tri-glucosides (IQ-G1′, IQ-G2′, and IQ-G3′; atypical IQ-Gs (IQ-Gap)) were synthesized through the reaction of amylosucrase. Here, the regio-selective transglycosylation yields were predicted using response surface methodology for three variables (glucose donor (sucrose; 100–1500 mM), glucose acceptor (IQ; 100–400 µM), and pH (5.0–8.8)) using 1 unit/mL of enzyme at 45 °C; then, the optima were verified according to the experimental responses. Acidity (pH 5.0) was a major contributor for IQ-G1′ production (> 50%), and high sucrose concentration (1500 mM) limited IQ-G3′ production (< 15%). Low sucrose concentration (100 mM) at pH 7.0 promoted higher glycosyl IQ production (> 30%). Time-course production of IQ-Gap showed an exponential growth with different rates. IQ-Gap was stable under the simulated intestinal conditions compared with typical IQ-Gs. Digestive stable IQ-Gap can be effectively synthesized by modulating reaction conditions; thereby, atypical glycosyl products may contribute to the elucidation of nutraceutical potential of flavonoid glycosides.
Key Points
•Predictions of RSM were validated for the regio-selective IQ-G ap production.
• Time course changes of IQ-G ap indicate non-processive glycosylation of DGAS.
• IQ-G ap exceed typical IQ-G in digestive stability at simulated intestinal condition.
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All data generated during this study are included in the paper or in the electronic supplementary material. Additional raw data are available from the authors upon request.
References
Amini M, Younesi H, Bahramifar N, Lorestani AA, Ghorbani F, Daneshi A, Sharifzadeh M (2008) Application of response surface methodology for optimization of lead biosorption in an aqueous solution by Aspergillus niger. J Hazard Mater 154(1–3):694–702. https://doi.org/10.1016/j.jhazmat.2007.10.114
Bokkenheuser VD, Shackleton CH, Winter J (1987) Hydrolysis of dietary flavonoid glycosides by strains of intestinal Bacteroides from humans. Biochem J 248(3):953–956. https://doi.org/10.1042/bj2480953
Chan KS, Greaves SJ, Rahardja S (2019) Techniques for addressing saddle points in the response surface methodology (RSM). IEEE Access 7:85613–85621. https://doi.org/10.1109/ACCESS.2019.2922975
Chiorcea-Paquim AM, Enache TA, De Souza GE, Oliveira-Brett AM (2020) Natural phenolic antioxidants electrochemistry: towards a new food science methodology. Compr Rev Food Sci Food Saf 19(4):1680–1726. https://doi.org/10.1111/1541-4337.12566
Choi SH, Kim HS, Yoon YJ, Kim D-M, Lee EY (2012) Glycosyltransferase and its application to glycodiversification of natural products. J Ind Eng Chem 18(4):1208–1212. https://doi.org/10.1016/j.jiec.2012.01.048
Goh LM, Barlow PJ (2004) Flavonoid recovery and stability from Ginkgo biloba subjected to a simulated digestion process. Food Chem 86(2):195–202. https://doi.org/10.1016/j.foodchem.2003.08.035
Hur HG, Lay JO Jr, Beger RD, Freeman JP, Rafii F (2000) Isolation of human intestinal bacteria metabolizing the natural isoflavone glycosides daidzin and genistin. Arch Microbiol 174(6):422–428. https://doi.org/10.1007/s002030000222
Jeya M, Zhang Y-W, Kim I-W, Lee J-K (2009) Enhanced saccharification of alkali-treated rice straw by cellulase from Trametes hirsuta and statistical optimization of hydrolysis conditions by RSM. Bioresour Technol 100(21):5155–5161. https://doi.org/10.1016/j.biortech.2009.05.040
Kulkarni SS, Wang C-C, Sabbavarapu NM, Podilapu AR, Liao PH, Hung SC (2018) “One-pot” protection, glycosylation, and protection−glycosylation strategies of carbohydrates. Chem Rev 118(17):8025–8104. https://doi.org/10.1021/acs.chemrev.8b00036
Lee YS, Woo JB, Ryu SI, Moon SK, Han NS, Lee SB (2017) Glucosylation of flavonol and flavanones by Bacillus cyclodextrin glucosyltransferase to enhance their solubility and stability. Food Chem 229:75–83. https://doi.org/10.1016/j.foodchem.2017.02.057
Letona CAM, Park CS, Kim YR (2017) Amylosucrase-mediated β-carotene encapsulation in amylose microparticles. Biotechnol Prog 33(6):1640–1646. https://doi.org/10.1002/btpr.2521
Li H, Kim UH, Yoon JH, Ji HS, Park HM, Park HY, Jeong TS (2019) Suppression of hyperglycemia and hepatic steatosis by black-soybean-leaf extract via enhanced adiponectin-receptor signaling and AMPK activation. J Agric Food Chem 67(1):90–101. https://doi.org/10.1021/acs.jafc.8b04527
Li R, Yuan C, Dong C, Shuang S, Choi MM (2011) In vivo antioxidative effect of isoquercitrin on cadmium-induced oxidative damage to mouse liver and kidney. Naunyn Schmiedebergs Arch Pharmacol 383(5):437–445. https://doi.org/10.1007/s00210-011-0613-2
Makino T, Shimizu R, Kanemaru M, Suzuki Y, Moriwaki M, Mizukami H (2009) Enzymatically modified isoquercitrin, α-oligoglucosyl quercetin 3-O-glucoside, is absorbed more easily than other quercetin glycosides or aglycone after oral administration in rats. Biol Pharm Bull 32(12):2034–2040. https://doi.org/10.1248/bpb.32.2034
Johnson KA, Goody RS (2011) The original Michaelis constant: translation of the 1913 Michaelis−Menten paper. Biochemistry 50(39):8264–8269. https://doi.org/10.1021/bi201284u
Minekus M, Alminger M, Alvito P, Ballance S, Bohn T, Bourlieu C, Carriere F, Boutrou R, Corredig M, Dupont D, Dufour C, Egger L, Golding M, Karakaya S, Kirkhus B, Le Feunteun S, Lesmes U, Macierzanka A, Mackie A, Marze S, McClements DJ, Menard O, Recio I, Santos CN, Singh RP, Vegarud GE, Wickham MS, Weitschies W, Brodkorb A (2014) A standardised static in vitro digestion method suitable for food - an international consensus. Food Funct 5(6):1113–1124. https://doi.org/10.1039/c3fo60702j
Monchois V, Willemot RM, Monsan P (1999) Glucansucrases: mechanism of action and structure-function relationships. FEMS Microbiol Rev 23(2):131–151. https://doi.org/10.1111/j.1574-6976.1999.tb00394.x
Murota K, Matsuda N, Kashino Y, Fujikura Y, Nakamura T, Kato Y, Shimizu R, Okuyama S, Tanaka H, Koda T, Sekido K, Terao J (2010) α-Oligoglucosylation of a sugar moiety enhances the bioavailability of quercetin glucosides in humans. Arch Biochem Biophys 501(1):91–97. https://doi.org/10.1016/j.abb.2010.06.036
O’brien RM (2007) A caution regarding rules of thumb for variance inflation factors. Qual Quant 41(5):673–690. https://doi.org/10.1007/s11135-006-9018-6
Penninga D, Strokopytov B, Rozeboom HJ, Lawson CL, Dijkstra BW, Bergsma J, Dijkhuizen L (1995) Site-directed mutations in tyrosine 195 of cyclodextrin glycosyltransferase from Bacillus circulans strain 251 affect activity and product specificity. Biochemistry 34(10):3368–3376. https://doi.org/10.1021/bi00010a028
Peričin D, Radulović-Popović L, Vaštag Ž, Mađarev-Popović S, Trivić S (2009) Enzymatic hydrolysis of protein isolate from hull-less pumpkin oil cake: application of response surface methodology. Food Chem 115(2):753–757. https://doi.org/10.1016/j.foodchem.2008.12.040
Qi Q, Zimmermann W (2005) Cyclodextrin glucanotransferase: from gene to applications. Appl Microbiol Biotechnol 66(5):475–485. https://doi.org/10.1007/s00253-004-1781-5
Rha C-S, Choi JM, Jung YS, Kim E-R, Ko MJ, Seo D-H, Kim D-O, Park C-S (2019a) High-efficiency enzymatic production of α-isoquercitrin glucosides by amylosucrase from Deinococcus geothermalis. Enzyme Microb Technol 120:84–90. https://doi.org/10.1016/j.enzmictec.2018.10.006
Rha C-S, Jung YS, Seo D-H, Kim D-O, Park C-S (2019b) Site-specific α-glycosylation of hydroxyflavones and hydroxyflavanones by amylosucrase from Deinococcus geothermalis. Enzyme Microb Technol 129:109361. https://doi.org/10.1016/j.enzmictec.2019.109361
Rha C-S, Kim HG, Baek N-I, Kim D-O, Park C-S (2020a) Amylosucrase from Deinococcus geothermalis can be modulated under different reaction conditions to produce novel quercetin 4′-O-α-D-isomaltoside. Enzyme Microb Technol 141:109648. https://doi.org/10.1016/j.enzmictec.2020.109648
Rha C-S, Kim HG, Baek N-I, Kim D-O, Park C-S (2020b) Using amylosucrase for the controlled synthesis of novel isoquercitrin glycosides with different glycosidic linkages. J Agric Food Chem 68:13798–13805. https://doi.org/10.1021/acs.jafc.0c05625
Rha C-S, Seong H, Jung YS, Jang D, Kwak JG, Kim D-O, Han NS (2019c) Stability and fermentability of green tea flavonols in in-vitro-simulated gastrointestinal digestion and human fecal fermentation. Int J Mol Sci 20(23):5890. https://doi.org/10.3390/ijms20235890
Robyt JF (1995) Mechanisms in the glucansucrase synthesis of polysaccharides and oligosaccharides from sucrose. Adv Carbohydr Chem Biochem 51:133–168. https://doi.org/10.1016/s0065-2318(08)60193-6
Rogerio AP, Kanashiro A, Fontanari C, da Silva EV, Lucisano-Valim YM, Soares EG, Faccioli LH (2007) Anti-inflammatory activity of quercetin and isoquercitrin in experimental murine allergic asthma. Inflamm Res 56(10):402–408. https://doi.org/10.1007/s00011-007-7005-6
Seo D-H, Yoo S-H, Choi S-J, Kim Y-R, Park C-S (2020) Versatile biotechnological applications of amylosucrase, a novel glucosyltransferase. Food Science and Biotechnology 29(1):1–16. https://doi.org/10.1007/s10068-019-00686-6
Spínola V, Llorent-Martínez EJ, Castilho PC (2018) Antioxidant polyphenols of Madeira sorrel (Rumex maderensis): how do they survive to in vitro simulated gastrointestinal digestion? Food Chem 259:105–112. https://doi.org/10.1016/j.foodchem.2018.03.112
Tacias-Pascacio VG, Torrestiana-Sánchez B, Dal Magro L, Virgen-Ortíz JJ, Suárez-Ruíz FJ, Rodrigues RC, Fernandez-Lafuente R (2019) Comparison of acid, basic and enzymatic catalysis on the production of biodiesel after RSM optimization. Renew Energy 135:1–9. https://doi.org/10.1016/j.renene.2018.11.107
Tonkova A (1998) Bacterial cyclodextrin glucanotransferase. Enzyme Microb Technol 22(8):678–686. https://doi.org/10.1016/s0141-0229(97)00263-9
Veitch NC, Grayer RJ (2011) Flavonoids and their glycosides, including anthocyanins. Nat Prod Rep 28(10):1626–1695. https://doi.org/10.1039/c1np00044f
Walsh R, Martin E, Darvesh S (2010) A method to describe enzyme-catalyzed reactions by combining steady state and time course enzyme kinetic parameters. Biochim Biophys Acta 1800(1):1–5. https://doi.org/10.1016/j.bbagen.2009.10.007
Wang W, Chen F, Zheng F, Russell BT (2020) Optimization of synthesis of carbohydrates and 1-phenyl-3-methyl-5-pyrazolone (PMP) by response surface methodology (RSM) for improved carbohydrate detection. Food Chem 309:125686. https://doi.org/10.1016/j.foodchem.2019.125686
Xiao J, Muzashvili TS, Georgiev MI (2014) Advances in the biotechnological glycosylation of valuable flavonoids. Biotechnol Adv 32(6):1145–1156. https://doi.org/10.1016/j.biotechadv.2014.04.006
Acknowledgements
We are grateful to Dr. N. S. Han, Professor of Chungbuk National University, Cheongju, Republic of Korea, for kindly supplying the in vitro digestion method.
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C-S.R: conceptualization, formal analysis, methodology, resources, software, validation, visualization, writing—original draft preparation, and writing—reviewing and editing. C-S.P: resources and writing—reviewing. D-O.K: resources, data curation, and writing—reviewing. All authors read and approved the manuscript.
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The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: C-S.R declares employment with AMOREPACIFIC Corporation and tested the experimental procedure and evaluation tools in this study; C-S.P and D-O.K, who are members of the Industry-Academic Cooperation Foundation of Kyung Hee University, declare that there is right of invention which was applied to the patent (title, preparation method of flavonol 3-isoglycosides; application number, 10-–2019-0163522 KR) for the newly synthesized IQ-Gap.
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Rha, CS., Park, CS. & Kim, DO. Optimized enzymatic synthesis of digestive resistant anomalous isoquercitrin glucosides using amylosucrase and response surface methodology. Appl Microbiol Biotechnol 105, 6931–6941 (2021). https://doi.org/10.1007/s00253-021-11532-3
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DOI: https://doi.org/10.1007/s00253-021-11532-3