A Cheminformatics Analysis Of Natural Products From Different Biological Sources

Natural products?NPs?refer to the secondary metabolites produced by natural organisms?including animals,plants and microorganisms,etc.?and have a wide range of biological activities.Due to structural diversity,NPs have been playing an important role in drug development.53%of chemical medicines come from NPs and derivatives.Analysis of the structural diversity and chemical space of NPs can help us know better the relationship among NPs,biological evolution and environmental pressure,and promote NP-based drug development.In order to study the structure and property differences of NPs from different biological sources,a comparative cheminformatics analysis was conducted on NPs from animals,plants and microorganisms.First,metainformation were collected from the Dictionary of Natural Products?DNP?,including structures,biological sources and type of compound.DNP annotates the source information of 186679 NPs,of which 68.36%come from plants,19.39%from microorganisms and 12.24%from animals.In DNP,out of the 201881 NPs with type of compound information,terpenoids?33.80%?and alkaloids?16.43%?are the two most abundant chemical classes.Based on Sugar Buster,we devised a process for glycosyl recognition.Sugar or sugar-like moieties of NPs were removed with this algorithm.It is found that 16.77%of NPs contain such moieties.The proportions of glycosylated NPs from plants,microorganisms and animals decrease successively,which are 25.52%,13.35%and8.79%respectively.Then,we analysed the relationship between biological sources and chemical classes of NPs.Most of the compounds have multiple biological sources.Some of them have obvious species bias distribution.For example,polyketides?76.68%?mainly come from microorganism-derived NPs.Terpenoids and polyphenolic compounds?tannins,flavonoids and lignin?are primarily from plant-derived NPs.Tannins are almost exclusively found in dicotyledons?99.01%?.Flavonoids?83.77%?and lignin?83.68%?are more widely from dicotyledons,followed by monocotyledons?7.96%and 7.12%respectively?.Finally,a comparative analysis of physicochemical properties and scaffold characteristics of NPs from diverse biological sources was conducted.And the chemical space was visualized by Tree Map and SAR Map.The results show that animal-derived NPs have more chiral centers,C³_sp atoms and rotatable bonds,indicating that animal-derived NPs have higher three-dimensional complexity.The molecular weight and molecular surface area of NPs from microorganisms and animals are higher than those from plants,suggesting that animal-derived NPs and microorganism-derived NPs are larger.Results of scaffold analysis show that NPs derived from animals and microorganisms have more large rings,while plant-derived NPs have more five-or six-membered rings.It demonstrates that plant-derived NPs are more structurally stable.In addition,more nitrogen atoms,oxygen atoms and sulfur atoms are found in microorganism-derived NPs,illustrating that NPs from microorganisms may be synthesized by more diverse biosynthetic pathways.In conclusion,NPs with different biological sources in DNP were compared and analyzed in terms of chemical classes,physicochemical properties,molecular fragments and chemical space.Deep excavation and analysis of these data can provide guidance to the discovery of NPs,and promote the development of new NP-based drugs.