Virtual screening and docking analysis of novel ligands for selective enhancement of tea (Camellia sinensis) flavonoids

Anusha Majumder; Sunil Kanti Mondal; Samyabrata Mukhoty; Sagar Bag; Anupam Mondal; Yasmin Begum; Kalpna Sharma; Avishek Banik

doi:10.1016/j.fochx.2022.100212

Virtual screening and docking analysis of novel ligands for selective enhancement of tea (Camellia sinensis) flavonoids

Food Chem X. 2022 Jan 18:13:100212. doi: 10.1016/j.fochx.2022.100212. eCollection 2022 Mar 30.

Authors

Anusha Majumder¹, Sunil Kanti Mondal², Samyabrata Mukhoty², Sagar Bag¹, Anupam Mondal¹, Yasmin Begum^{3

4}, Kalpna Sharma⁵, Avishek Banik¹

Affiliations

¹ Laboratory of Microbial Interaction, School of Biotechnology, Presidency University, Kolkata, West Bengal, India.
² Department of Biotechnology, The University of Burdwan, Burdwan, West Bengal, India.
³ Department of Biophysics, Molecular Biology, and Bioinformatics, University of Calcutta, 92, APC Road, Kolkata 700009, West Bengal, India.
⁴ Center of Excellence in Systems Biology and Biomedical Engineering (TEQIP Phase-III), University of Calcutta, JD-2, Sector III, Salt Lake, Kolkata 700106, West Bengal, India.
⁵ R&D Centre, Danguajhar Tea Garden, Goodricke Group Ltd., Jalpaiguri, West Bengal, India.

Abstract

Flavour of tea is mainly contributed by a group of polyphenols - flavonoids. However, the content of flavonoid fluctuates seasonally and is found to be higher in the first flush of tea, when compared to the second flush. This disparity in the flavonoid content, and hence taste, incurs heavy economic losses to the tea plantation industry each harvest season. For our present study, four key product-specific enzymes (PAL, FNS, FLS and ANS) of the tea-specific flavonoid pathway were selected to perform molecular docking studies with specific virtually screened allosteric modulators. Results of docking analyses showed Naringenin, 2-Morpholin-4-ium-4-ylethanesulfonate, 6-C-Glucosylquercetin, 2-Oxoglutaric acid, 3,5,7,3',4'-pentahydroxyflavone to be capable of improving the spontaneity of the enzyme-substrate reactions in terms of docking score, RMSD values, and non-covalent interactions (H-bond,hydrophobic interaction, Π-stacking, salt bridge, etc.). Further, the evolutionary relationship of tea flavonoid pathway enzymes was constructed and compared with related taxa. The codon usage-based of tea flavonoid biosynthetic genes indicated the non-biasness of their nucleotide composition. Overall this study will provide a direction towards putative ligand-dependent enhancement of flavonoid content, irrespective of seasonal variation.

Keywords: 4CL, Tyrosine ammonia lyase; AMF, Arbuscular Mycorrhizal Fungi; ANR, anthocyanidin reductase; ANS, anthocyanidinsynthase; C4H, trans-cinnamate-4-; CAI, Codon Adaptation Index; CHI, chalcone isomerase; CHS, 4-coumarat; CoA, ligase chalcone synthase; Codon usage indices; DFR, dihydroflavonol 4-reductase; ENc, Effective number of codons; F3H, flavanone 3-hydroxylase; F3′5′H, flavonoid 3′5′-hydroxylase; F3′H, flavonoid 3′-hydroxylase; FLS, Flavonol synthase; FNS, flavone synthase; Flavonoids; GC1, GC2, and GC3-GC, content at the first, second, and third codon positions; GC3s, frequency of either G or C at the third codon position of synonymous codons; H 0, null hypothesisno selection; IAA, Indole acetic acid; LAR, leucoanthocyanidin reductase; Ligands; Molecular docking; PAL, phenylalanine ammonia-lyase; RMSD, root-mean-square deviation; RSCU, Relative Synonymous Codon Usage; TAL, monooxygenase; Tea flush; UGT72, UDP-3 glycosyltransferases; Virtual screening.