Highlighting glycosylation ways in Caryophyllaceae saponins by simplex simulation approach

Graphical Abstract Abstract. Glycosylation mechanisms in saponins of Caryophyllaceae plant family were subjected to simulation by statistically exploring variability of 231 chemical structures belonging to four different aglycones: gypsogenin ( Gyp ), quillaic acid ( QA ), gypsogenic acid ( GA ), 16-OH-gypsogenic acid (16-OH- GA ). Saponins based on different aglycones were initially characterized by relative glycosylation levels of different carbons. Simulation was initialized by combining the four saponin groups using Scheffé’s mixture design which provides a complete set of N gradual weightings of groups. Combined saponins were randomly and iteratively sampled from different groups by bootstrap technique. For a same combination, saponins were averaged leading to barycentric glycosylation profile. Iterations of the N barycentric profiles and averaging provided a final response matrix of N smoothed glycosylation profiles from which regulation mechanisms of carbons were highlighted in different aglycone-based saponins. Glucose ( Glc ) was revealed to be widely favored in GA and 16-OH- GA with more target Gyp and QA showed higher regulations of with affinity Ara , Xyl ) and 16-OH- GA for Xyl , 28- Ara ). These results call for further investments in simulations of glycosylation mechanisms helping for better understanding metabolic aspects of saponins, and encouraging future analytic experiments in the field.


Graphical Abstract
Abstract.
Glycosylation mechanisms in saponins of Caryophyllaceae plant family were subjected to simulation by statistically exploring variability of 231 chemical structures belonging to four different aglycones: gypsogenin (Gyp), quillaic acid (QA), gypsogenic acid (GA), 16-OHgypsogenic acid (16-OH-GA). Saponins based on different aglycones were initially characterized by relative glycosylation levels of different carbons. Simulation was initialized by combining the four saponin groups using Scheffé's mixture design which provides a complete set of N gradual weightings of groups. Combined saponins were randomly and iteratively sampled from different groups by bootstrap technique. For a same combination, saponins were averaged leading to barycentric glycosylation profile. Iterations of the N barycentric profiles and averaging provided a final response matrix of N smoothed glycosylation profiles from which regulation mechanisms of carbons were highlighted in different aglycone-based saponins. Glucose (Glc) was revealed to be widely favored in GA and 16-OH-GA with more target aspect of 28-Glc in 16-OH-GA and relatively shared distribution between C28 (mainly) C3 and C23 in GA. Strong competition for galactose (Gal) was highlighted between C3 and C28 with target aspects to 28-Gal in GA and 3-Gal in (Gyp, QA). Gyp and QA showed higher regulations of pentoses (xylose, Xyl; arabinose, Ara) with more affinity of GA for (3-Ara, 28-Xyl) and 16-OH-GA for (3-Xyl, 28-Ara). These results call for further investments in simulations of glycosylation mechanisms helping for better understanding metabolic aspects of saponins, and encouraging future analytic experiments in the field.  Laabidi et al., 2018). For that aim, simulation simplex approach was applied to a bibliographic set of 231 Caryophyllaceae saponins to highlight aglycone-and carbon-dependent glycosylation mechanism for different saccharides.

Materials and Method. A whole set of 231 saponins was initially organized into 4 aglycone subsets:
Gyp, QA, GA,80,52,20 saponins,respectively) (Cheikh Ali et al., 2019). Saponins were characterized by their glycosylation (Gly) regulation profiles containing relative occurrence degrees of different saccharides at different carbons (Sarraj et al., 2018). Gly profiles of saponins were iteratively combined by applying Scheffé's mixture design giving a complete set of N gradual weights for the q (=4) groups (Scheffé, 1958). At the output of N iterated combinations, N barycentric Glyprofiles were calculated resulting in smoothed data that were used for graphical analysis of regulation trends between different saccharides at different carbons under different aglycones (Fig. 1).
Results. Glc strongly characterized GA and 16-OH-GA saponins whereas Gyp and QA showed higher diversification of glycosylation at the expense of Glc. GA and 16-OH-GA were functionally differentiated by distributional and target aspects of Glc, respectively (Fig. 1). In GA, Glc was shared between C28 (60%), C3 (12%) and C23 (5%), whereas in 16-OH-GA, Glc was mainly target to C28 (80%). Gyp and QA were less concerned with Glc with low regulation levels (< 3%). This could indicate interactions between aglycone type and carbon position on regulation levels of Glc. Concerning Gal, GA showed relatively higher trend of 28-Gal whereas 16-OH-GA did not favor galactosylation at all the carbons. However, Gyp and QA showed target mechanism of 3-Gal at the expense of 28-Gal. Pentoses (Xyl, Ara) manifested in Gyp and QA vs negligible levels in GA and 16-OH-GA. Gyp and QA were differentiated by glycosylation positions: 28-Xyl and 3-Ara were relatively more favored in Gyp, vs 28-Ara and 3-Xyl in QA. http://sciforum.net/conference/mol2net-05

Conclusion.
Simulation results could be indicative of differential regioselectivities concerning different saccharide types varying at both inter-molecular (between sapogenins) and intra-molecular (between carbons) scales.