Too sweet: cheminformatics for deglycosylation in natural products

Abstract

Sugar units in natural products are pharmacokinetically important but often redundant and therefore obstructing the study of the structure and function of the aglycon. Therefore, it is recommended to remove the sugars before a theoretical or experimental study of a molecule. Deglycogenases, enzymes that specialized in sugar removal from small molecules, are often used in laboratories to perform this task. However, there is no standardized computational procedure to perform this task in silico. In this work, we present a systematic approach for in silico removal of ring and linear sugars from molecular structures. Particular attention is given to molecules of biological origin and to their structural specificities. This approach is made available in two forms, through a free and open web application and as standalone open-source software.

COCONUT online: Collection of Open Natural Products database

“…For this reason, NPs in COCONUT have been analysed for sugar moieties presence, and a deglycosylated structure representation was made available in the database. Sugar moieties manipulations were performed using the Sugar Removal Utility [ 21 ]. To track their influence on other features, their absence and presence are colour-mapped (no sugar moiety in the molecular structure in blue, and the presence of at least one sugar moiety in orange).…”

“…AfroCancer 365 [33] AfroDB 874 [34] AfroMalariaDB 252 [35] AnalytiCon Discovery NPs 4908 [36] BIOFACQUIM 400 [37] BitterDB 625 [38] Carotenoids Database 986 [39] ChEBI NPs 14603 [20] ChEMBL NPs 1585 [21] ChemSpider NPs 9027 [40] CMAUP (cCollective molecular activities of useful plants) 20868 [7] ConMedNP 2504 [41] ETM (Ethiopian Traditional Medicine) DB 1633 [42] Exposome-explorer 478 [43] FooDB 22123 [9] GNPS (Global Natural Products Social Molecular Networking) 6740 [44] HIM (Herbal Ingredients in-vivo Metabolism database) 962 [45] HIT (Herbal Ingredients Targets) 470 [46] Indofine Chemical Company 46 [47] InflamNat 536 [48] InPACdb 122 [49] InterBioScreen Ltd 67291 [50] KNApSaCK 44422 [6] Lichen Database 1453 [51] Marine Natural Products 11880 [52] Mitishamba database 1010 [53] NANPDB (Natural Products from Northern African Sources) 3914 [54] NCI DTP data 404 [55] NPACT 1453 [56] NPASS 27424 [57] NPAtlas 23914 [4] NPCARE 1362 [58] NPEdia 16166 [59] NuBBEDB 2022 [5] p-ANAPL 467 [60] Phenol-explorer 681 [61] PubChem NPs 2828 [27] ReSpect 699 [62] SANCDB 592 [63] Seaweed Metabolite Database (SWMD) 348 [64] Specs Natural Products 745…”

The Three Pillars of Natural Product Dereplication. Alkaloids from the Bulbs of Urceolina peruviana (C. Presl) J.F. Macbr. as a Preliminary Test Case

“…The rather ubiquitous α- and β- d -glucopyranose molecular sub-units are identified as 01-01-14-005 and -006, respectively. The idea of searching for sugars in NPs was put into practice recently in the framework of the COCONUT NP database development and the possible in silico deglycosylation [ 43 ]. The CL1 data items in PNMRNP include the lists of atoms concerned by each detected substructure.…”

Machine Learning Methods to Predict the Terrestrial and Marine Origin of Natural Products

“…In order to understand if there is the same distribution of NPs with sugar units in the data set within the three classes, MNPs, TNPs and B, the six Sub FPs (SubFP281‐SubFP286, based on six sugar SMART patterns) of the PaDEL‐Descriptor software were used to identify the NPs with sugar units. The Sugar Removal Utility application (https://sugar.naturalproducts.net/) was used to identify and remove terminal sugar units, both ring and linear [19] . The chemical diversity of the data set, training and test sets in accordance with the three classes, MNPs, TNPs and B was exploited using the following three characteristics: molecular weight (MW), XLogP (an estimation of the octanol‐water partition coefficient, Log P), and the presence of terminal sugar units.…”