How do biocatalysis and biotransformation affect Citrus dietary flavonoids chemistry and bioactivity? A review

References

• Mabberley D. Citrus (Rutaceae): a review of recent advances in etymology, systematics and medical applications. Blumea-Biodiversity. Blum – J Plant Tax and Plant Geog. 2004;49(2):481–498.
   Google Scholar
• García-Salas P, Gómez-Caravaca AM, Arráez-Román D, et al. Influence of technological processes on phenolic compounds, organic acids, furanic derivatives, and antioxidant activity of whole-lemon powder. Food Chem. 2013;141(2):869–878.
   PubMed Web of Science ®Google Scholar
• He D, Shan Y, Wu Y, et al. Simultaneous determination of flavanones, hydroxycinnamic acids and alkaloids in citrus fruits by HPLC-DAD–ESI/MS. Food Chem. 2011;127(2):880–885.
   PubMed Web of Science ®Google Scholar
• Lv X, Zhao S, Ning Z, et al. Citrus fruits as a treasure trove of active natural metabolites that potentially provide benefits for human health. Chem Cent J. 2015;9(1):68.
   PubMedGoogle Scholar
• Wang L, Wang J, Fang L, et al. Anticancer activities of citrus peel polymethoxyflavones related to angiogenesis and others. BioMed Res Int. 2014;2014:1–10.
   Web of Science ®Google Scholar
• Manthey JA, Grohmann K. Phenols in citrus peel byproducts. Concentrations of hydroxycinnamates and polymethoxylated flavones in citrus peel molasses. J Agric Food Chem. 2001;49(7):3268–3273.
   PubMed Web of Science ®Google Scholar
• Ejaz S, Ejaz A, Matsuda K, et al. Limonoids as cancer chemopreventive agents. J Sci Food Agric. 2006;86(3):339–345.
   Web of Science ®Google Scholar
• Tripoli E, Guardia ML, Giammanco S, et al. Citrus flavonoids: molecular structure, biological activity and nutritional properties: a review. Food Chem. 2007;104(2):466–479.
   Web of Science ®Google Scholar
• Horowitz R, Gentili B. Dihydrochalcone sweeteners from citrus flavanones in “Alternative Sweetners., Nabors LO and Gelardi RC, eds. 1986. New York (NY): Marcel Dekker, Inc.
   Google Scholar
• Hultin PG. Bioactive C-glycosides from bacterial secondary metabolism. Curr Topic Med Chem. 2005;5(14):1299–1331.
   PubMed Web of Science ®Google Scholar
• Frydman A, Liberman R, Huhman DV, et al. The molecular and enzymatic basis of bitter/non‐bitter flavor of citrus fruit: evolution of branch‐forming rhamnosyltransferases under domestication. Plant J. 2013;73(1):166–178.
   PubMed Web of Science ®Google Scholar
• Sharma K, Mahato N, Lee YR. Extraction, characterization and biological activity of citrus flavonoids. Reviews Chem Eng. 2019;35(2):265–284.
   Web of Science ®Google Scholar
• Li S, Lo C-Y, Ho C-T. Hydroxylated polymethoxyflavones and methylated flavonoids in sweet orange (Citrus sinensis) peel. J Agric Food Chem. 2006;54(12):4176–4185.
   PubMed Web of Science ®Google Scholar
• Londoño-Londoño J, Lima V. R d, Lara O, et al. Clean recovery of antioxidant flavonoids from citrus peel: optimizing an aqueous ultrasound-assisted extraction method. Food Chem. 2010;119(1):81–87.
   Web of Science ®Google Scholar
• Walle T. Methylation of dietary flavones increases their metabolic stability and chemopreventive effects. Int J Mol Sci. 2009;10(11):5002–5019.
   PubMed Web of Science ®Google Scholar
• Tumbas V, Cetkovic G, Djilas S, et al. Antioxidant activity of mandarin (Citrus reticulata) peel. Acta per Tech. 2010;41(41):195–203.,
   Google Scholar
• Hayat K. Citrus molecular phylogeny antioxidant properties and medicinal uses. Nova Sci. 2014;3:235.
   Google Scholar
• Gattuso G, Barreca D, Gargiulli C, et al. Flavonoid composition of citrus juices. Molecules. 2007;12(8):1641–1673.
   PubMed Web of Science ®Google Scholar
• Panche A, Diwan A, Chandra S. Flavonoids: an overview. J Nutr Sci. 2016;5:e47.
   PubMed Web of Science ®Google Scholar
• Ruiz-Cruz S, Chaparro-Hernández S, Hernández-Ruiz KL, et al. Flavonoids: important biocompounds in food. Flavonoids-From Biosynthesis Human Health. 2017;16:353–364.
   Google Scholar
• Benavente-García O, Castillo J, Marin FR, et al. Uses and properties of citrus flavonoids. J Agric Food Chem. 1997;45(12):4505–4515.
   Web of Science ®Google Scholar
• Dontas AS, Zerefos NS, Panagiotakos DB, et al. Mediterranean diet and prevention of coronary heart disease in the elderly. Clin Inter Aging. 2007;2(1):109–109.
   PubMed Web of Science ®Google Scholar
• Cao H, Chen X, Jassbi AR, et al. Microbial biotransformation of bioactive flavonoids. Biotechnol Adv. 2015;33(1):214–223.
   PubMed Web of Science ®Google Scholar
• Hollman PCH, Katan MB. Dietary flavonoids: intake, health effects and bioavailability. Food Chem Toxicol. 1999;37(9–10):937–942.
   PubMed Web of Science ®Google Scholar
• Kumar S, Pandey AK. Chemistry and biological activities of flavonoids: an overview. Sci World J. 2013;2013:1–16.
   Google Scholar
• Liu X, Lin C, Ma X, et al. Functional characterization of a flavonoid glycosyltransferase in sweet orange (Citrus sinensis). Front Plant Sci. 2018;9:166.
   PubMed Web of Science ®Google Scholar
• Vogt T, Jones P. Glycosyltransferases in plant natural product synthesis: characterization of a supergene family. Trends Plant Sci. 2000;5(9):380–386.
   PubMed Web of Science ®Google Scholar
• Li Y, Baldauf S, Lim E-K, et al. Phylogenetic analysis of the UDP-glycosyltransferase multigene family of Arabidopsis thaliana. J Biol Chem. 2001;276(6):4338–4343.
   PubMed Web of Science ®Google Scholar
• Chang T-S, Wu J-Y, Wang T-Y, et al. Uridine diphosphate-dependent glycosyltransferases from Bacillus subtilis ATCC 6633 catalyze the 15-O-glycosylation of ganoderic acid A. Int J Mol Sci. 2018;19(11):3469.
   PubMed Web of Science ®Google Scholar
• Lewinsohn E, Berman E, Mazur Y, et al. (7) Glucosylation and (1–6) Rhamnosylation of exogenous flavanones by undifferentiated Citrus cell cultures. Plant Sci. 1989;61(1):23–28.
   Web of Science ®Google Scholar
• Frydman A, Weisshaus O, Bar-Peled M, et al. Citrus fruit bitter flavors: isolation and functional characterization of the gene Cm1, 2RhaT encoding a 1, 2 rhamnosyltransferase, a key enzyme in the biosynthesis of the bitter flavonoids of citrus. Plant J. 2004;40(1):88–100.
   PubMed Web of Science ®Google Scholar
• Plaza M, Pozzo T, Liu J, et al. Substituent effects on in vitro antioxidizing properties, stability, and solubility in flavonoids. J Agric Food Chem. 2014;62(15):3321–3333.
   PubMed Web of Science ®Google Scholar
• Rao SR, Ravishankar G. Plant cell cultures: chemical factories of secondary metabolites. Biotechnol Adv. 2002;20(2):101–153.
   PubMed Web of Science ®Google Scholar
• Suman S. Plant tissue culture: a promising tool of quality material production with special reference to micropropagation of banana. Biochem. Cell. Arch. 2017;17(1):1–26.
   Google Scholar
• Ochoa-Villarreal M, Howat S, Hong SMi, et al. Plant cell culture strategies for the production of natural products. BMB Reports. 2016;49(3):149–158.
   PubMed Web of Science ®Google Scholar
• Shimoda K, Kubota N, Taniuchi K, et al. Biotransformation of naringin and naringenin by cultured Eucalyptus perriniana cells. Phytochemistry. 2010;71(2–3):201–205.
   PubMed Web of Science ®Google Scholar
• Hamada H, Tanaka T, Furuya T, et al. Hydroxylation of benzylic and allylic sites by plant cultured suspension cells. Tetrahedron Lett. 2001;42(5):909–911.
   Web of Science ®Google Scholar
• Hussain MB, Hassan S, Waheed M, et al. Bioavailability and metabolic pathway of phenolic compounds. In plant physiological aspects of phenolic compounds. IntechOpen; 2019. p. 1–18.
   Google Scholar
• Mansell R, McIntosh C. Citrus spp.: in vitro culture and the production of naringin and limonin, in Medicinal and Aromatic Plants III. McIntosh: Springer; 1991. p. 193–210.
   Google Scholar
• Gerolino EF, Chierrito TPC, Filho AS, et al. Evaluation of limonoid production in suspension cell culture of Citrus sinensis. Revista Brasileira de Farmacognosia. 2015;25(5):455–461.
   Google Scholar
• Del Río J, Ortuño A. Citrus paradisi Macf.(Grapefruit): in vitro culture and the bioproduction of sesquiterpenes nootkatone, valencene, and other secondary metabolites, in Medicinal and Aromatic Plants VII. McIntosh: Springer; 1994. p. 123–138.
   Google Scholar
• Shimoda K, Hamada H, Hamada H. Glycosylation of hesperetin by plant cell cultures. Phytochemistry. 2008;69(5):1135–1140.
   PubMed Web of Science ®Google Scholar
• Shimoda K, Sato N, Kobayashi T, et al. Glycosylation of daidzein by the Eucalyptus cell cultures. Phytochemistry. 2008;69(12):2303–2306.
   PubMed Web of Science ®Google Scholar
• Hosoda R, Horio Y, Shimoda K, et al. Regioselective hydroxylation and glucosylation of flavanones with cultured plant cells of Eucalyptus perriniana. Nat Prod Commun. 2013;8(7):1934578X1300800.
   Web of Science ®Google Scholar
• Salehi B, Fokou P, Sharifi-Rad M, et al. The therapeutic potential of naringenin: a review of clinical trials. Pharmaceuticals. 2019;12(1):11.
   Web of Science ®Google Scholar
• Walle T, Browning AM, Steed LL, et al. Flavonoid glucosides are hydrolyzed and thus activated in the oral cavity in humans. J Nutri. 2005;135(1):48–52.
   PubMed Web of Science ®Google Scholar
• Kottra G, Daniel H. Flavonoid glycosides are not transported by the human Na+/glucose transporter when expressed in Xenopus laevis oocytes, but effectively inhibit electrogenic glucose uptake. J Pharmacol Exp Ther. 2007;322(2):829–835.
   PubMed Web of Science ®Google Scholar
• Chen Y, Wang J, Jia X, et al. Role of intestinal hydrolase in the absorption of prenylated flavonoids present in Yinyanghuo. Molecules. 2011;16(2):1336–1348.
   PubMed Web of Science ®Google Scholar
• Xiao J. Dietary flavonoid aglycones and their glycosides: which show better biological significance? Crit Rev Food Sci Nutr. 2015;57(9):1874–1905.
   Web of Science ®Google Scholar
• Day AJ, Cañada FJ, Dı́az JC, et al. Dietary flavonoid and isoflavone glycosides are hydrolysed by the lactase site of lactase phlorizin hydrolase. FEBS Lett. 2000;468(2–3):166–170. p.
   PubMed Web of Science ®Google Scholar
• Gee JM, DuPont MS, Day AJ, et al. Intestinal transport of quercetin glycosides in rats involves both deglycosylation and interaction with the hexose transport pathway. J Nutri. 2000;130(11):2765–2771.
   PubMed Web of Science ®Google Scholar
• Qin J, Li R, Raes J, et al. A human gut microbial gene catalogue established by metagenomic sequencing. Nature. 2010;464(7285):59–65.
   PubMed Web of Science ®Google Scholar
• Schloissnig S, Arumugam M, Sunagawa S, et al. Genomic variation landscape of the human gut microbiome. Nature. 2013;493(7430):45–50.
   PubMed Web of Science ®Google Scholar
• Valentová K, Vrba J, Bancířová M, et al. Isoquercitrin: pharmacology, toxicology, and metabolism. Food Chem Toxicol. 2014;68:267–282.
   PubMed Web of Science ®Google Scholar
• Manach C, Morand C, Texier O, et al. Quercetin metabolites in plasma of rats fed diets containing rutin or quercetin. J Nutri. 1995;125(7):1911–1922.
   PubMed Web of Science ®Google Scholar
• Hollman P, Katan M. Absorption, metabolism and health effects of dietary flavonoids in man. Biomed Pharmacother. 1997;51(8):305–310.
   PubMed Web of Science ®Google Scholar
• Amaretti A, Raimondi S, Leonardi A, et al. Hydrolysis of the rutinose-conjugates flavonoids rutin and hesperidin by the gut microbiota and bifidobacteria. Nutrients. 2015;7(4):2788–2800.
   PubMed Web of Science ®Google Scholar
• Braune A, Blaut M. Bacterial species involved in the conversion of dietary flavonoids in the human gut. Gut Microbes. 2016;7(3):216–234.
   PubMed Web of Science ®Google Scholar
• Braune A, Gutschow M, Engst W, et al. Degradation of quercetin and luteolin byEubacterium ramulus. Appl Environ Microbiol. 2001;67(12):5558–5567.
   PubMed Web of Science ®Google Scholar
• Schoefer L, Mohan R, Schwiertz A, et al. Anaerobic degradation of flavonoids by Clostridium orbiscindens. Appl Environ Microbiol. 2003;69(10):5849–5854.
   PubMed Web of Science ®Google Scholar
• Pereira-Caro G, Ludwig IA, Polyviou T, et al. Identification of plasma and urinary metabolites and catabolites derived from orange juice (poly) phenols: analysis by high-performance liquid chromatography–high-resolution mass spectrometry. J Agric Food Chem. 2016;64(28):5724–5735.
   PubMed Web of Science ®Google Scholar
• Zeng X, Su W, Zheng Y, et al. Pharmacokinetics, tissue distribution, metabolism, and excretion of naringin in aged rats. Front Pharmacol. 2019;10:34.
   PubMed Web of Science ®Google Scholar
• Slámová K, Kapešová J, Valentová K. “Sweet flavonoids”: glycosidase-catalyzed modifications. Int J Mol Sci. 2018;19(7):2126.
   PubMed Web of Science ®Google Scholar
• Chanet A, Milenkovic D, Claude S, et al. Flavanone metabolites decrease monocyte adhesion to TNF-α-activated endothelial cells by modulating expression of atherosclerosis-related genes. Br J Nutr. 2013;110(4):587–598.
   PubMed Web of Science ®Google Scholar
• Yamamoto M, Jokura H, Hashizume K, et al. Hesperidin metabolite hesperetin-7-O-glucuronide, but not hesperetin-3′-O-glucuronide, exerts hypotensive, vasodilatory, and anti-inflammatory activities. Food Funct. 2013;4(9):1346–1351.
   PubMed Web of Science ®Google Scholar
• Giménez-Bastida JA, González-Sarrías A, Vallejo F, et al. Hesperetin and its sulfate and glucuronide metabolites inhibit TNF-α induced human aortic endothelial cell migration and decrease plasminogen activator inhibitor-1 (PAI-1) levels. Food Funct. 2016;7(1):118–126.
   PubMed Web of Science ®Google Scholar
• Mullen W, Archeveque M-A, Edwards CA, et al. Bioavailability and metabolism of orange juice flavanones in humans: impact of a full-fat yogurt. J Agric Food Chem. 2008;56(23):11157–11164.
   PubMed Web of Science ®Google Scholar
• Bredsdorff L, Nielsen ILF, Rasmussen SE, et al. Absorption, conjugation and excretion of the flavanones, naringenin and hesperetin from α-rhamnosidase-treated orange juice in human subjects. Br J Nutr. 2010;103(11):1602–1609.
   PubMed Web of Science ®Google Scholar
• Pereira-Caro G, Borges G, van der Hooft J, et al. Orange juice (poly)phenols are highly bioavailable in humans. Am J Clin Nutri. 2014;100(5):1378–1384.
   PubMed Web of Science ®Google Scholar
• Pereira-Caro G, Oliver CM, Weerakkody R, et al. Chronic administration of a microencapsulated probiotic enhances the bioavailability of orange juice flavanones in humans. Free Radical Biol Med. 2015;84:206–214.
   PubMed Web of Science ®Google Scholar
• Stevens Y, Rymenant EV, Grootaert C, et al. The intestinal fate of citrus flavanones and their effects on gastrointestinal health. Nutrients. 2019;11(7):1464.
   Web of Science ®Google Scholar
• Takumi H, Nakamura H, Simizu T, et al. Bioavailability of orally administered water-dispersible hesperetin and its effect on peripheral vasodilatation in human subjects: implication of endothelial functions of plasma conjugated metabolites. Food Funct. 2012;3(4):389–398.
   PubMed Web of Science ®Google Scholar
• Gamo K, Shiraki T, Matsuura N, et al. Mechanism of peroxisome proliferator-activated receptor gamma (PPARγ) transactivation by hesperetin glucuronides is distinct from that by a thiazolidine-2, 4-dione agent. Chem Pharm Bull. 2014;62(5):491–493.
   PubMed Web of Science ®Google Scholar
• Manach C, Morand C, Gil-Izquierdo A, et al. Bioavailability in humans of the flavanones hesperidin and narirutin after the ingestion of two doses of orange juice. Eur J Clin Nutr. 2003;57(2):235–242.
   PubMed Web of Science ®Google Scholar
• Brett GM, Hollands W, Needs PW, et al. Absorption, metabolism and excretion of flavanones from single portions of orange fruit and juice and effects of anthropometric variables and contraceptive pill use on flavanone excretion. Br J Nutr. 2008;101(5):664–675.
   Web of Science ®Google Scholar
• Felgines C, Texier O, Morand C, et al. Bioavailability of the flavanone naringenin and its glycosides in rats. Am J Phys-Gastr Liver Physiol. 2000;279(6):G1148–G1154.
   PubMed Web of Science ®Google Scholar
• Benković G, Bojić M, Maleš Ž, et al. Screening of flavonoid aglycons’ metabolism mediated by the human liver cytochromes P450. Acta Pharmaceutica. 2019;69(4):541–562.
   PubMed Web of Science ®Google Scholar
• Nielsen SE, Breinholt V, Cornett C, et al. Biotransformation of the citrus flavone tangeretin in rats. Identification of metabolites with intact flavane nucleus. Food Chem Toxicol. 2000;38(9):739–746.
   PubMed Web of Science ®Google Scholar
• Wei G-J, Chao Y-H, Tung Y-C, et al. A tangeretin derivative inhibits the growth of human prostate cancer LNCaP cells by epigenetically restoring p21 gene expression and inhibiting cancer stem-like cell proliferation. Aaps J. 2019;21(5):86.
   PubMed Web of Science ®Google Scholar
• Koga N, Ohta C, Kato Y, et al. In vitro metabolism of nobiletin, a polymethoxy-flavonoid, by human liver microsomes and cytochrome P450. Xenobiotica. 2011;41(11):927–933.
   PubMed Web of Science ®Google Scholar
• Li S, Wang Z, Sang S, et al. Identification of nobiletin metabolites in mouse urine. Mol Nutr Food Res. 2006;50(3):291–299.
   PubMed Web of Science ®Google Scholar
• Murakami A, Koshimizu K, Ohigashi H, et al. Characteristic rat tissue accumulation of nobiletin, a chemopreventive polymethoxyflavonoid, in comparison with luteolin. Biofactors. 2002;16(3–4):73–82.
   PubMed Web of Science ®Google Scholar
• Yasuda T, Yoshimura Y, Yabuki H, et al. Urinary metabolites of nobiletin orally administered to rats. Chem Pharm Bull. 2003;51(12):1426–1428.
   PubMed Web of Science ®Google Scholar
• Li B, Smith B, Hossain MM. Extraction of phenolics from citrus peels: II. Enzyme-Assisted Extract Method. Separat Purificat Technol. 2006;48(2):189–196.
   Web of Science ®Google Scholar
• Koga N, Matsuo M, Ohta C, et al. Comparative study on nobiletin metabolism with liver microsomes from rats, guinea pigs and hamsters and rat cytochrome P450. Biol Pharm Bull. 2007;30(12):2317–2323.
   PubMed Web of Science ®Google Scholar
• Zheng J, Bi J, Johnson D, et al. Analysis of 10 metabolites of polymethoxyflavones with high sensitivity by electrochemical detection in high-performance liquid chromatography. J Agric Food Chem. 2015;63(2):509–516.
   PubMed Web of Science ®Google Scholar
• Zheng J, Song M, Dong P, et al. Identification of novel bioactive metabolites of 5‐demethylnobiletin in mice. Mol Nutr Food Res. 2013;57(11):1999–2007.
   PubMed Web of Science ®Google Scholar
• Song M, Charoensinphon N, Wu X, et al. Inhibitory effects of metabolites of 5-demethylnobiletin on human nonsmall cell lung cancer cells. J Agric Food Chem. 2016;64(24):4943–4949.
   PubMed Web of Science ®Google Scholar
• Macer DR. Perception of risks and benefits of in vitro fertilization, genetic engineering and biotechnology. Soc Sci Med. 1994;38(1):23–33.
   PubMed Web of Science ®Google Scholar
• Ravindran S, Basu S, Surve P, et al. In vitro biotransformation in drug discovery. Concepts to Market. 2018;1:1–13.
   Google Scholar
• Pereira-Caro G, Fernández-Quirós B, Ludwig IA, et al. Catabolism of citrus flavanones by the probiotics Bifidobacterium longum and Lactobacillus rhamnosus. Eur J Nutr. 2018;57(1):231–242.
   PubMed Web of Science ®Google Scholar
• Kim M, Kim N, Han J. Metabolism of Kaempferia parviflora polymethoxyflavones by human intestinal bacterium Bautia sp. MRG-PMF1. J Agric Food Chem. 2014;62(51):12377–12383.
   PubMed Web of Science ®Google Scholar
• Burapan S, Kim M, Han J. Demethylation of polymethoxyflavones by human gut bacterium, Blautia sp. MRG-PMF1. J Agric Food Chem. 2017;65(8):1620–1629.
   PubMed Web of Science ®Google Scholar
• Kay CD, Pereira-Caro G, Ludwig IA, et al. Anthocyanins and flavanones are more bioavailable than previously perceived: a review of recent evidence. Annu Rev Food Sci Technol. 2017;8(1):155–180.,
   PubMedGoogle Scholar
• Kim D-H, Jung E-A, Sohng I-S, et al. Intestinal bacterial metabolism of flavonoids and its relation to some biological activities. Arch Pharm Res. 1998;21(1):17–23.
   PubMed Web of Science ®Google Scholar
• Lin S, Zhu Q, Wen L, et al. Production of quercetin, kaempferol and their glycosidic derivatives from the aqueous-organic extracted residue of litchi pericarp with Aspergillus awamori. Food Chem. 2014;145:220–227.
   PubMed Web of Science ®Google Scholar
• Hosny M, Dhar K, Rosazza JP. Hydroxylations and Methylations of Quercetin, Fisetin, and Catechin by Streptomyces g riseus. J Nat Prod. 2001;64(4):462–465.
   PubMed Web of Science ®Google Scholar
• Wang Y-y, Liu J-h, Yu B-y. Biotransformation of Flavonoids by Streptomyces griseus ATCC 13273. Pharm Biotechnol-Beijing. 2005;12(5):308.
   Google Scholar
• Walle T. Methoxylated flavones, a superior cancer chemopreventive flavonoid subclass. Seminars Cancer Biol. 2007;17(5):354–362.
   PubMed Web of Science ®Google Scholar
• Bernini R, Crisante F, Ginnasi MC. A convenient and safe O-methylation of flavonoids with dimethyl carbonate (DMC). Molecules. 2011;16(2):1418–1425.
   PubMed Web of Science ®Google Scholar
• You HJ, Ahn HJ, Ji GE. Transformation of rutin to antiproliferative quercetin-3-glucoside by Aspergillus niger. J Agric Food Chem. 2010;58(20):10886–10892.
   PubMed Web of Science ®Google Scholar
• Okuno Y, Miyazawa M. Biotransformation of Nobiletin by Aspergillus n iger and the Antimutagenic Activity of a Metabolite, 4′-Hydroxy-5, 6, 7, 8, 3′-pentamethoxyflavone. J Nat Prod. 2004;67(11):1876–1878.
   PubMed Web of Science ®Google Scholar
• Okuno Y, Miyazawa M. Microbial O‐demethylation of sinesetin and antimutagenic activity of the metabolite. J Chem Technol Biotechnol. 2006;81(1):29–33.
   Web of Science ®Google Scholar
• Buisson D, Quintin J, Lewin G. Biotransformation of polymethoxylated flavonoids: access to their 4′-O-demethylated metabolites. J Nat Prod. 2007;70(6):1035–1038.
   PubMed Web of Science ®Google Scholar
• Ibrahim A-RS, Galal AM, Ahmed MS, et al. O-demethylation and sulfation of 7-methoxylated flavanones by Cunninghamella elegans. Chem Pharmaceut Bulletin. 2003;51(2):203–206.
   PubMed Web of Science ®Google Scholar
• Kimura J, Nemoto K, Yokosuka A, et al. 6-Demethoxynobiletin, a nobiletin-analog citrus flavonoid, enhances extracellular signal-regulated kinase phosphorylation in PC12D cells. Biolog Pharmaceut Bulletin. 2013;36(10):1646–1649.
   PubMed Web of Science ®Google Scholar
• Esaki H, Watanabe R, Onozaki H, et al. Formation mechanism for potent antioxidative o-dihydroxyisoflavones in soybeans fermented with Aspergillus saitoi. Biosci Biotechno Biochem. 1999;63(5):851–858.
   PubMed Web of Science ®Google Scholar
• Miyake Y, Minato K, Fukumoto S, et al. New potent antioxidative hydroxyflavanones produced with Aspergillus saitoi from flavanone glycoside in citrus fruit. Biosci Biotechnol Biochem. 2003;67(7):1443–1450.
   PubMed Web of Science ®Google Scholar
• Osawa T, Minato K, Miyake Y. Flavonoid compound and process for producing the same. 2009. Google Patents.
   Google Scholar
• Miyake Y, Minato K-I, Fukumoto S, et al. Radical-scavenging activity in vitro of lemon peel fermented with Aspergillus saitoi and its suppressive effect against exercise-induced oxidative damage in rat liver. Food Sci Techno Res. 2004;10(1):70–74.
   Web of Science ®Google Scholar
• Kim G-N, Shin J-G, Jang H-D. Antioxidant and antidiabetic activity of Dangyuja (Citrus grandis Osbeck) extract treated with Aspergillus saitoi. Food Chem. 2009;117(1):35–41.
   Web of Science ®Google Scholar
• Ruviaro AR, Barbosa PdPM, Macedo GA. Enzyme-assisted biotransformation increases hesperetin content in citrus juice by-products. Food Res Int. 2019;124:213–221.
   PubMed Web of Science ®Google Scholar
• HöLker U, HöFer M, Lenz J. Biotechnological advantages of laboratory-scale solid-state fermentation with fungi. Appl Microbiol Biotechnol. 2004;64(2):175–186.
   PubMed Web of Science ®Google Scholar
• Johannes TW, Zhao H. Directed evolution of enzymes and biosynthetic pathways. Curr Opin Microbiol. 2006;9(3):261–267.
   PubMed Web of Science ®Google Scholar
• Kumar A, Singh S. Directed evolution: tailoring biocatalysts for industrial applications. Crit Rev Biotechnol. 2013;33(4):365–378.
   PubMed Web of Science ®Google Scholar
• Carboué Q. Production of microbial enzymes by solid state fermentation for food applications. Microbial Enzyme Technol Food App. 2017;24:437–451.
   Google Scholar
• Murakami A, Ashida H, Terao J. Multitargeted cancer prevention by quercetin. Cancer Lett. 2008;269(2):315–325.
   PubMed Web of Science ®Google Scholar
• Mazzaferro LS, Breccia JD. Quantification of hesperidin in citrus-based foods using a fungal diglycosidase. Food Chem. 2012;134(4):2338–2344.
   PubMed Web of Science ®Google Scholar
• Piñuel L, Breccia JD, Guisán JM, et al. Production of hesperetin using a covalently multipoint immobilized diglycosidase from Acremonium sp. DSM24697. J Mol Microbiol Biotechnol. 2013;23(6):410–417.
   PubMed Web of Science ®Google Scholar
• Zhu Y, Jia H, Xi M, et al. Purification and characterization of a naringinase from a newly isolated strain of Bacillus amyloliquefaciens 11568 suitable for the transformation of flavonoids. Food Chem. 2017;214:39–46.
   PubMed Web of Science ®Google Scholar
• Busto MD, Meza V, Ortega N, et al. Immobilization of naringinase from Aspergillus niger CECT 2088 in poly (vinyl alcohol) cryogels for the debittering of juices. Food Chem. 2007;104(3):1177–1182.
   Web of Science ®Google Scholar
• Lee Y-S, Huh J-Y, Nam S-H, et al. Enzymatic bioconversion of citrus hesperidin by Aspergillus sojae Naringinase: enhanced solubility of hesperetin-7-O-glucoside with in vitro inhibition of human intestinal maltase, HMG-CoA reductase, and growth of Helicobacter pylori. Food Chem. 2012;135(4):2253–2259.
   PubMed Web of Science ®Google Scholar
• Nielsen ILF, Chee WSS, Poulsen L, et al. Bioavailability is improved by enzymatic modification of the citrus flavonoid hesperidin in humans: a randomized, double-blind, crossover trial. J Nutr. 2006;136(2):404–408.
   PubMed Web of Science ®Google Scholar
• Madeira JV, Nakajima VM, Macedo JA, et al. Rich bioactive phenolic extract production by microbial biotransformation of Brazilian Citrus residues. Chem Eng Res Des. 2014;92(10):1802–1810.
   Web of Science ®Google Scholar
• Ferreira LR, Macedo JA, Ribeiro ML, et al. Improving the chemopreventive potential of orange juice by enzymatic biotransformation. Food Res Int. 2013;51(2):526–535.
   Web of Science ®Google Scholar
• da Silva CMG, Contesini FJ, Sawaya ACHF, et al. Enhancement of the antioxidant activity of orange and lime juices by flavonoid enzymatic de-glycosylation. Food Res Int. 2013;52(1):308–314.
   Web of Science ®Google Scholar
• Kaur A, Singh S, Singh RS, et al. Hydrolysis of citrus peel naringin by recombinant α‐L‐rhamnosidase from Clostridium stercorarium. J Chem Technol Biotechnol. 2010;85(10):1419–1422.
   Web of Science ®Google Scholar
• Alvarenga AE, Romero CM, Castro GR. A novel α-L-rhamnosidase with potential applications in citrus juice industry and in winemaking. Eur Food Res Technol. 2013;237(6):977–985.
   Web of Science ®Google Scholar
• Yadav S. Orange peel naringin hydrolyzed by αLrhamnosidase from Aspergillus flavipus MTCC4644. Int J Biolog Med Res. 2018;9(3):6400–6405.
   Google Scholar
• Li L, Gong J, Wang S, et al. Heterologous expression and characterization of a new clade of aspergillus α-L-Rhamnosidase suitable for citrus juice processing. J Agric Food Chem. 2019;67(10):2926–2935.
   PubMed Web of Science ®Google Scholar
• Mandalari G, Bennett RN, Kirby AR, et al. Enzymatic hydrolysis of flavonoids and pectic oligosaccharides from bergamot (Citrus bergamia Risso) peel. J Agric Food Chem. 2006;54(21):8307–8313.
   PubMed Web of Science ®Google Scholar
• Madeira JV, Jr, Macedo JA, Macedo GA, et al. Efficient tannase production using Brazilian citrus residues and potential application for orange juice valorization. Biocatal Agric Biotechnol. 2015;4(1):91–97.
   Web of Science ®Google Scholar
• Madeira JV, Speranza P, Macedo GA. Phenolic compounds and tannase production by solid-state fermentation in orange pomace. New Biotechnol. 2012;29:S94.
   Web of Science ®Google Scholar
• Madeira JV, Macedo JA, Macedo GA. A new process for simultaneous production of tannase and phytase by Paecilomyces variotii in solid-state fermentation of orange pomace. Bioprocess Biosyst Eng. 2012;35(3):477–482.
   PubMed Web of Science ®Google Scholar
• Li Y-m, Li X-m, Li G-m, et al. In vivo pharmacokinetics of hesperidin are affected by treatment with glucosidase-like BglA protein isolated from yeasts. J Agric Food Chem. 2008;56(14):5550–5557.
   PubMed Web of Science ®Google Scholar
• Shin K-C, Nam H-K, Oh D-K. Hydrolysis of flavanone glycosides by β-glucosidase from Pyrococcus furiosus and its application to the production of flavanone aglycones from citrus extracts. J Agric Food Chem. 2013;61(47):11532–11540.
   PubMed Web of Science ®Google Scholar
• Muzna S, Divya D, Kamat SD, et al. Antifungal activity of lipase modified flavonoids from citrus limetta. Int J Pharm Pharm Sci. 2014;6:116–118.
   Google Scholar
• Heim KE, Tagliaferro AR, Bobilya DJ. Flavonoid antioxidants: chemistry, metabolism and structure-activity relationships. J Nutri Biochem. 2002;13(10):572–584.
   PubMed Web of Science ®Google Scholar
• Nakajima VM, Madeira JV, Macedo GA, et al. Biotransformation effects on anti lipogenic activity of citrus extracts. Food Chem. 2016;197:1046–1053.
   PubMed Web of Science ®Google Scholar
• Farag MA, Huhman DV, Dixon RA, et al. Metabolomics reveals novel pathways and differential mechanistic and elicitor-specific responses in phenylpropanoid and isoflavonoid biosynthesis in Medicago truncatula cell cultures. Plant Physiol. 2008;146(2):387–402.
   PubMed Web of Science ®Google Scholar
• Sahota P, Kaur N. Characterization of enzyme naringinase and the production of debittered low alcoholic kinnow (Citrus raticulata blanco) beverage. Int J Adv Res. 2015;36:1220–1233.
   Google Scholar
• Chen Y, Ni H, Chen F, et al. Purification and characterization of a naringinase from Aspergillus aculeatus JMUdb058. J Agric Food Chem. 2013;61(4):931–938.
   PubMed Web of Science ®Google Scholar
• Kuivanen J, Richard P. Engineering a filamentous fungus for L-rhamnose extraction. AMB Expr. 2016;6(1):27.
   PubMedGoogle Scholar
• Celiz G, Audisio MC, Daz M. Antimicrobial properties of prunin, a citric flavanone glucoside, and its prunin 6 ″‐O‐lauroyl ester. J App Microbiol. 2010;109(4):1450–1457.
   PubMed Web of Science ®Google Scholar
• Madeira Junior JV. Tannase production and phenolic compounds obtainment by biotransformation of Paecilomyces variotii from Citrus residues = Produção de tanase e obtenção de compostos fenólicos através da biotransformação por Paecilomyces variotii a partir de resíduos de Citrus. 2014.
   Google Scholar
• Yang Y, Bai L, Li X, et al. Transport of active flavonoids, based on cytotoxicity and lipophilicity: an evaluation using the blood–brain barrier cell and Caco-2 cell models. Toxicol in Vitro. 2014;28(3):388–396.
   PubMed Web of Science ®Google Scholar
• Veleva RK, Moskova-Doumanova V, Todorova M, et al. Cytotoxicity of flavonoid glycosides, flavonoids and phenolic acids from Inula oculus-christi on mammalian cell lines. J BioSci Biotechno. 2016;5(3):219–224.
   Google Scholar
• Katsoura MH, Polydera AC, Katapodis P, et al. Effect of different reaction parameters on the lipase-catalyzed selective acylation of polyhydroxylated natural compounds in ionic liquids. Process Biochem. 2007;42(9):1326–1334.
   Web of Science ®Google Scholar
• Breinholt VM, Rasmussen SE, Brosen K, et al. In vitro metabolism of genistein and tangeretin by human and murine cytochrome P450s. Pharmacol Toxicol. 2003;93(1):14–22.
   PubMedGoogle Scholar
• Nielsen SE, Breinholt V, Justesen U, et al. In vitro biotransformation of flavonoids by rat liver microsomes. Xenobiotica. 1998;28(4):389–401.
   PubMed Web of Science ®Google Scholar
• Breinholt VM, Offord EA, Brouwer C, et al. In vitro investigation of cytochrome P450-mediated metabolism of dietary flavonoids. Food Chem Toxicol. 2002;40(5):609–616.
   PubMed Web of Science ®Google Scholar
• Rafiq S, Kaul R, Sofi SA, et al. Citrus peel as a source of functional ingredient: a review. J Saudi Soc Agric Sci. 2018;17(4):351–358.
   Google Scholar
• Almeida JR, Modig T, Petersson A, et al. Increased tolerance and conversion of inhibitors in lignocellulosic hydrolysates by Saccharomyces cerevisiae. J Chem Technol Biotechnol. 2007;82(4):340–349.
   Web of Science ®Google Scholar
• Koutinas M, Patsalou M, Stavrinou S, et al. High temperature alcoholic fermentation of orange peel by the newly isolated thermotolerant Pichia kudriavzevii KVMP 10. Lett Appl Microbiol. 2016;62(1):75–83.
   PubMed Web of Science ®Google Scholar
• Patsalou M, Samanides CG, Protopapa E, et al. A citrus peel waste biorefinery for ethanol and methane production. Molecules. 2019;24(13):2451.
   Web of Science ®Google Scholar
• Siles JA, Vargas F, Gutiérrez MC, et al. Integral valorisation of waste orange peel using combustion, biomethanisation and co-composting technologies. Bioresour Technol. 2016;211:173–182.
   PubMed Web of Science ®Google Scholar
• Mishra D, Shukla AK, Dixit AK, et al. Aqueous enzymatic extraction of oil from mandarin peels. J Oleo Sci. 2005;54(6):355–359.
   Google Scholar
• Chávez-González ML, López-López LI, Rodríguez-Herrera R, et al. Enzyme-assisted extraction of citrus essential oil. Chemical Papers. 2016;70(4):412–417.
   Web of Science ®Google Scholar
• Ahmed I, Zia MA, Hussain MA, et al. Bioprocessing of citrus waste peel for induced pectinase production by Aspergillus niger;its purification and characterization. J Radiat Res Appl Sci. 2016;9(2):148–154.
   Web of Science ®Google Scholar
• Kroeze JHA. Neohesperidin dihydrochalcone is not a taste enhancer in aqueous sucrose solutions. Chemical Senses. 2000;25(5):555–559.
   PubMed Web of Science ®Google Scholar
• Janvier S, Goscinny S, Donne CL, et al. Low-calorie sweeteners in food and food supplements on the Italian market. Food Addit Contam: Part B. 2015;8(4):150925162021009–150925162021308.
   Google Scholar
• Frydman A, Weisshaus O, Huhman DV, et al. Metabolic engineering of plant cells for biotransformation of hesperedin into neohesperidin, a substrate for production of the low-calorie sweetener and flavor enhancer NHDC. J Agric Food Chem. 2005;53(25):9708–9712.
   PubMed Web of Science ®Google Scholar
• Houlmont J-P, Vercruysse K, Perez E, et al. Cosmetic use formulations containing pentyl rhamnoside and cetyl rhamnoside. Int J Cosmet Sci. 2001;23(6):363–368.
   PubMedGoogle Scholar
• Vila-Real H, Alfaia AJ, Bronze MR, et al. Enzymatic synthesis of the flavone glucosides, prunin and isoquercetin, and the aglycones, naringenin and quercetin, with selective-l-rhamnosidase and-d-glucosidase activities of naringinase. Enzyme Res. 2011;2011:1–11.
   Google Scholar
• Puri M, Kaur A, Singh RS, et al. Immobilized enzyme technology for debittering citrus fruit juices. Food Enzymes: App New Techno. 2008;5:91–103.
   Google Scholar
• Salas MP, Céliz G, Geronazzo H, et al. Antifungal activity of natural and enzymatically-modified flavonoids isolated from citrus species. Food Chem. 2011;124(4):1411–1415.
   Web of Science ®Google Scholar
• Wu X, Song M, Qiu P, et al. Nobiletin and atorvastatin synergistically inhibit azoxymethane (AOM)-induced colon carcinogenesis in rats. The FASEB J. 2015;29(1_supplement):271–272.
   Google Scholar
• Wu X, Song M, Qiu P, et al. A metabolite of nobiletin, 4′-demethylnobiletin and atorvastatin synergistically inhibits human colon cancer cell growth by inducing G0/G1 cell cycle arrest and apoptosis. Food Funct. 2018;9(1):87–95.
   PubMed Web of Science ®Google Scholar