Analysis Of Glycosylation Characteristics Of Polyphenolic Natural Products

Polyphenolic natural products,accounting for about 20% of natural products,are a series of compounds that posses an aromatic ring with at least one hydroxyl group.The main classes of polyphenolic natural products includes flavonoids,tannins,lignans,phenolic acids and other polyphenols.Previous studies have reported that polyphenolic natural products had a higher proportion of glycosylation than other natural products.In order to investigate the characteristics and understand the biological significance of glycosylation of polyphenolic natural products,a comprehensive study was carried out in this paper.Here in the species origin,structural subclasses,and glycosylation characteristics of flavonoids,tannins,lignans,phenolic acids and other polyphenols were analyzed carefully.Firstly,the biological source and proportion of glycosylation of polyphenolic natural products were analyzed.The results showed that polyphenolic natural products were mainly derived from Dicotyledonous plants.31.17% of flavonoids can be extracted from Legumes.Tannins were abundant in Euphorbiaceae(15.16%)and Fagaceae(12.57%).Lignans,phenolic acids and other polyphenols were widely distributed in the biological universe.Glycosidic ratio of flavonoids,tannins,lignans,phenolic acids and other polyphenols was39.21%,44.78%,22.44%,27.58% and 7.96%,respectively.The results indicated that glycosidic ratio of polyphenols was different.Thus,further studies should be conducted to characterize the polyphenols by categories.Secondly,the glycosidic characteristics of polyphenolic natural glycosides were analyzed.Monohexose was the most frequently occurred substituent of polyphenolic natural glycosides.The most common glycosyl unit was glucose,fucose and pentopyranose.Glycosyl substitution occured mainly on the hydroxyl group of aglycones.Therefore,the dominat linkage between aglycones and glycosyl was O-glycosidic bond.The glycosylation of flavonoids were located at C-3 and C-7,while the glycosylation of tannins and phenolic acids were located at the carboxyl groups.Then,the random forest models were developed to discriminate the glycosides from non glycosides,and aglycones from non glycosides after deduplication.The data from COCONUT(Collection of Open Natural Products)were used as the external validation set.The accuracy of glycoside classification model reached 0.99,which manifested that the model has excellent predictive ability and can accurately identify sugar-containing molecules.However,it appeared to be difficult to discriminate aglycones and deduplicated non glycosides.The reason may be that the difference between the two types of molecular structures is subtle.Finally,the bioactive polyphenolic glycosides in Ch EMBL were analyzed.The proportion of glycosylation of active flavonoids and phenolic acids was much lower than that of DNP and COCONUT.It indicated that aglycones,rather than glycosyl,contributed to the physiological activities of these molecules.Intriguingly,53.85% of the active tannins were glycosides.In summary,this paper explored various glycosylation characteristics of five classes of polyphenols,including the distribution patterns of biological sources and structural subclasses,the characteristics of glycosides,the discrimination of glycosides,and the relationship between glycosidation and activity.The preference of polyphenol glycosidation in species and structure was revealed.The results presented in this paper may be used as a guidance in the extraction and synthesis of polyphenol glycosides.This study provided cheminformatics insights into the glycosylation of polyphenolic natural products and may promote the pharmacokinetic study of this class of compounds.