In this study, we investigated an efficient enzymatic strategy for producing potentially valuable phloretin metabolites from phlorizin, a glucoside of phloretin that is rich in apple pomace. Almond β-glucosidase efficiently removed phlorizin's glucose moiety to produce phloretin. CYP102A1 engineered by site-directed mutagenesis, domain swapping, and random mutagenesis catalyzed the highly regioselective C-hydroxylation of phloretin into 3-OH phloretin with high conversion yields. Under the optimal hydroxylation conditions of 15 g cells L and a 20 mM substrate for whole-cell biocatalysis, phloretin was regioselectively hydroxylated into 3.1 mM 3-OH phloretin each hour. Furthermore, differentiation of 3T3-L1 preadipocytes into adipocytes and lipid accumulation were dramatically inhibited by 3-OH phloretin but promoted by phloretin. Consistent with these inhibitory effects, the expression of adipogenic regulator genes was downregulated by 3-OH phloretin. We propose a platform for the sustainable production and value creation of phloretin metabolites from apple pomace capable of inhibiting adipogenesis.
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http://dx.doi.org/10.1021/acs.jafc.0c03156 | DOI Listing |
Molecules
February 2023
School of Biological Sciences and Technology, Chonnam National University, Gwangju 61186, Republic of Korea.
Phloretin and its glycoside phlorizin have been reported to prevent obesity induced by high-fat diet (HFD), but the effect of 3-OH phloretin, a catechol metabolite of phloretin, has not been investigated. In this study, we investigated the anti-obesity effects of phloretin and 3-OH phloretin in HFD-fed mice. The body weight gain induced by HFD was more inhibited by administration of 3-OH phloretin than by phloretin.
View Article and Find Full Text PDFToxicol Appl Pharmacol
January 2022
Department of Pharmacology, Maulana Abul Kalam Azad University of Technology, Simhat Haringhata, Nadia 741249, West Bengal, India.
Our recent investigation directed to synthesize a novel ruthenium-phloretin complex accompanied by the study of antioxidant in addition to DNA binding capabilities, to determine the chemotherapeutic activity against breast carcinoma in vitro and in vivo. Ruthenium-phloretin complex was synthesized and characterized by different spectroscopic methods. The complex was further investigated to determine its efficacy in both MCF-7 and MDA-MB-231 human carcinoma cell lines and finally in an in vivo model of mammary carcinogenesis induced by DMBA in rats.
View Article and Find Full Text PDFAntioxidants (Basel)
August 2021
School of Biological Sciences and Biotechnology, Graduate School, Chonnam National University, Yongbong-ro 77, Gwangju 61186, Korea.
Phlorizin is the most abundant glucoside of phloretin from the apple tree and its products. Phlorizin and its aglycone phloretin are currently considered health-beneficial polyphenols from apples useful in treating hyperglycemia and obesity. Recently, we showed that phloretin could be regioselectively hydroxylated to make 3-OH phloretin by CYP102A1 and human P450 enzymes.
View Article and Find Full Text PDFPharmaceuticals (Basel)
October 2020
School of Biological Sciences and Biotechnology, Graduate School, Chonnam National University, Yongbong-ro 77, Gwangju 61186, Korea.
Phloretin, the major polyphenol compound in apples and apple products, is interesting because it shows beneficial effects on human health. It is mainly found as a form of glucoside, phlorizin. However, the metabolic pathway of phloretin in humans has not been reported.
View Article and Find Full Text PDFJ Agric Food Chem
June 2020
School of Biological Sciences and Technology, Chonnam National University, 77 Yongbongro, Gwangju 61186, Republic of Korea.
In this study, we investigated an efficient enzymatic strategy for producing potentially valuable phloretin metabolites from phlorizin, a glucoside of phloretin that is rich in apple pomace. Almond β-glucosidase efficiently removed phlorizin's glucose moiety to produce phloretin. CYP102A1 engineered by site-directed mutagenesis, domain swapping, and random mutagenesis catalyzed the highly regioselective C-hydroxylation of phloretin into 3-OH phloretin with high conversion yields.
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