Structural Similarities and Overlapping Activities among Dihydroflavonol 4-Reductase, Flavanone 4-Reductase, and Anthocyanidin Reductase Offer Metabolic Flexibility in the Flavonoid Pathway
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Published:2023-09-09
Issue:18
Volume:24
Page:13901
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ISSN:1422-0067
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Container-title:International Journal of Molecular Sciences
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language:en
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Short-container-title:IJMS
Author:
Lewis Jacob A.1ORCID, Zhang Bixia1ORCID, Harza Rishi1ORCID, Palmer Nathan2, Sarath Gautam2, Sattler Scott E.2ORCID, Twigg Paul3, Vermerris Wilfred4ORCID, Kang ChulHee1ORCID
Affiliation:
1. Department of Chemistry, Washington State University, Pullman, WA 99164, USA 2. Wheat, Sorghum, Forage Research Unit, U.S. Department of Agriculture—Agricultural Research Service, Lincoln, NE 68583, USA 3. Biology Department, University of Nebraska at Kearney, Kearney, NE 68849, USA 4. Department of Microbiology & Cell Science and UF Genetics Institute, University of Florida, Gainesville, FL 32610, USA
Abstract
Flavonoids are potent antioxidants that play a role in defense against pathogens, UV-radiation, and the detoxification of reactive oxygen species. Dihydroflavonol 4-reductase (DFR) and flavanone 4-reductase (FNR) reduce dihydroflavonols and flavanones, respectively, using NAD(P)H to produce flavan-(3)-4-(di)ols in flavonoid biosynthesis. Anthocyanidin reductase (ANR) reduces anthocyanidins to flavan-3-ols. In addition to their sequences, the 3D structures of recombinant DFR, FNR and ANR from sorghum and switchgrass showed a high level of similarity. The catalytic mechanism, substrate-specificity and key residues of three reductases were deduced from crystal structures, site-directed mutagenesis, molecular docking, kinetics, and thermodynamic ana-lyses. Although DFR displayed its highest activity against dihydroflavonols, it also showed activity against flavanones and anthocyanidins. It was inhibited by the flavonol quercetin and high concentrations of dihydroflavonols/flavonones. SbFNR1 and SbFNR2 did not show any activity against dihydroflavonols. However, SbFNR1 displayed activity against flavanones and ANR activity against two anthocyanidins, cyanidin and pelargonidin. Therefore, SbFNR1 and SbFNR2 could be specific ANR isozymes without delphinidin activity. Sorghum has high concentrations of 3-deoxyanthocyanidins in vivo, supporting the observed high activity of SbDFR against flavonols. Mining of expression data indicated substantial induction of these three reductase genes in both switchgrass and sorghum in response to biotic stress. Key signature sequences for proper DFR/ANR classification are proposed and could form the basis for future metabolic engineering of flavonoid metabolism.
Funder
USDA-NIFA NSF Murdock Charitable Trust DOE Office of Science User Facility USDA-ARS CRIS projects
Subject
Inorganic Chemistry,Organic Chemistry,Physical and Theoretical Chemistry,Computer Science Applications,Spectroscopy,Molecular Biology,General Medicine,Catalysis
Reference77 articles.
1. Red Card for Pathogens: Phytoalexins in Sorghum and Maize;Poloni;Molecules,2014 2. Liu, W., Feng, Y., Yu, S., Fan, Z., Li, X., Li, J., and Yin, H. (2021). The Flavonoid Biosynthesis Network in Plants. Int. J. Mol. Sci., 22. 3. Structural Characterization of Wheat Straw Lignin as Revealed by Analytical Pyrolysis, 2D-NMR, and Reductive Cleavage Methods;Rencoret;J. Agric. Food Chem.,2012 4. Maize Tricin-Oligolignol Metabolites and Their Implications for Monocot Lignification;Lan;Plant Physiol.,2016 5. The Sorghum (Sorghum bicolor) Brown Midrib 30 Gene Encodes a Chalcone Isomerase Required for Cell Wall Lignification;Tetreault;Front. Plant Sci.,2021
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