A comprehensive review of glycosylated bacterial natural products

Abstract

A systematic analysis of all naturally-occurring glycosylated bacterial secondary metabolites reported in the scientific literature up through early 2013 is presented. This comprehensive analysis of 15 940 bacterial natural products revealed 3426 glycosides containing 344 distinct appended carbohydrates and highlights a range of unique opportunities for future biosynthetic study and glycodiversification efforts.

Fig. 1

Bacterial glycosylated (21.5%; 3426 compounds) and unglycosylated (78.5%; 12 514 compounds) natural products.

Fig. 2

Chemical classes of glycosylated bacterial natural products (total 3426 compounds).

Fig. 3

Summary of all sugars present in bacterial natural products (1–344). Only sugars that displayed differences within the fundamental monosaccharide core (specifically, notable stereochemical and/or functional group variation, including anomeric configuration) were considered as distinct. Modifications of a common sugar core (e.g., O/N/S-alkyl/acyl substitutions) were designated as identical to the parental core saccharide.

Fig. 3

Summary of all sugars present in bacterial natural products (1–344). Only sugars that displayed differences within the fundamental monosaccharide core (specifically, notable stereochemical and/or functional group variation, including anomeric configuration) were considered as distinct. Modifications of a common sugar core (e.g., O/N/S-alkyl/acyl substitutions) were designated as identical to the parental core saccharide.

Fig. 3

Summary of all sugars present in bacterial natural products (1–344). Only sugars that displayed differences within the fundamental monosaccharide core (specifically, notable stereochemical and/or functional group variation, including anomeric configuration) were considered as distinct. Modifications of a common sugar core (e.g., O/N/S-alkyl/acyl substitutions) were designated as identical to the parental core saccharide.

Fig. 3

Summary of all sugars present in bacterial natural products (1–344). Only sugars that displayed differences within the fundamental monosaccharide core (specifically, notable stereochemical and/or functional group variation, including anomeric configuration) were considered as distinct. Modifications of a common sugar core (e.g., O/N/S-alkyl/acyl substitutions) were designated as identical to the parental core saccharide.

Fig. 3

Summary of all sugars present in bacterial natural products (1–344). Only sugars that displayed differences within the fundamental monosaccharide core (specifically, notable stereochemical and/or functional group variation, including anomeric configuration) were considered as distinct. Modifications of a common sugar core (e.g., O/N/S-alkyl/acyl substitutions) were designated as identical to the parental core saccharide.

Fig. 4

Summary of pseudosugars P1–P28 present in bacterial natural products. This list represents only those pseudosugar found within the context of bacterial glycosides and does not reflect an exhaustive list of naturally-occurring pseudosugars.

Fig. 5

Pactamycin aglycons and associated pseudosugars.

Fig. 6

Aminoglycoside pseudosugars and associated sugars.

Fig. 7

The five major types in angucyclines and glycosylation positions.

Fig. 8

Landomycin aglycons and associated sugars.

Fig. 9

Saquayamycin aglycons and associated sugars.

Fig. 10

Urdamycin aglycons and associated sugars.

Fig. 11

Other related angucycline aglycons and associated sugars.

Fig. 12

Gilvocarcin and jadomycin aglycons and associated sugars.

Fig. 13

The five anthracycline sub-classes I–V and glycosylation positions.

Fig. 14

Sugars associated with anthracyclines.

Fig. 15

Disaccharide variations D1–D15 observed in anthracyclines.

Fig. 16

Trisaccharide variations (I–XXXV) observed in anthracyclines.

Fig. 17

Tetrasaccharide variations (T1–T8) observed in anthracyclines.

Fig. 18

Pentasaccharide variations P1–P2 observed in anthracyclines.

Fig. 19

Hibarimicin aglycons and associated sugars.

Fig. 20

Tetracycline aglycons and associated sugars.

Fig. 21

Aureolic acid analogs and associated sugars.

Fig. 22

Pyranonaphthoquinone related aglycons and associated sugars.

Fig. 23

Benzoquinone-related aglycons and associated sugars.

Fig. 24

Benanomicin and pradimicin aglycons and associated sugars.

Fig. 25

Chartarin aglycons and associated sugars.

Fig. 26

Coumarin aglycons and associated sugars.

Fig. 27

9-Membered enediyne aglycons and associated sugars. Ar, aromatic moiety.

Fig. 28

10-Membered enediyne aglycons and associated sugars. Ar, aromatic moiety.

Fig. 29

Flavonoid and isoflavonoid aglycons and associated sugars.

Fig. 30

Fused indole-related aglycons and associated sugars where different colors distinguish multiple points of attachment.

Fig. 31

Simple indole-related aglycons and associated sugars.

Fig. 32

Glycolipids, polyenes and carotenoids and associated sugars.

Fig. 33

12-, 14- and 16-membered macrolactones and associated sugars.

Fig. 34

18-, 20-, 22-, 24-Membered macrolactones and macrodiolides and associated sugars.

Fig. 35

Super macrolactone (ring size 32–48) aglycons and associated sugars.

Fig. 36

Polyene and macrolactam aglycons and associated sugars.

Fig. 37

Spirotetronates and spinosyn aglycons and associated sugars.

Fig. 38

Uracil-derived aglycons.

Fig. 39

Sugars associated with uracil-derived aglycons. Pink fragment is absent in some derivatives.

Fig. 40

Cytosine-derived aglycons and associated sugars.

Fig. 41

Purine-derived aglycons and associated sugars.

Fig. 42

Orsellinic acid aglycons and associated sugars.

Fig. 43

Sugars associated with orthoester aminocyclitols.

Fig. 44

Bleomycin aglycons and associated sugars. Platomycin structure is based on partial structure reported.

Fig. 45

Aglycons of the five types of vancomycin. The ether bridge in types III and IV is highlighted in red. Locataions of attachment to most sugars in CWI-785 series is not determined.

Fig. 46

Sugars associated with vancomycins.

Fig. 47

Mannopeptimycin, salmochelin, and salmomycin aglycons and associated sugars.

Fig. 48

Lincosamide and thiazolyl peptide aglycons and associated sugars. Indole moiety in red is absent or replaced by quinoline in different members.

Fig. 49

Lipoglycopeptide aglycons and associated sugars. Only partial structures of burkholdine, cepacidins, and herbicolin are shown.

Fig. 50

Miscellaneous antiinfective peptide aglycons and associated sugars.

Fig. 51

Miscellaneous peptide aglycons and associated sugars.

Fig. 52

Phenazine aglycons and associated sugars.

Fig. 53

Piericidin and pyranone aglycons and associated sugars.

Fig. 54

Pluramycin aglycons and associated sugars.

Fig. 55

Polyethers aglycons and associated sugars.

Fig. 56

Pterin aglycons and associated sugars.

Fig. 57

Streptothricin aglycons and associated sugars.

Fig. 58

Sesquiterpene and diterpene aglycons and associated sugars.

Fig. 59

Triterpenes aglycons and associated sugars.

Fig. 60

Trioxacarcins and LL-D49194 aglycons and associated sugars.

Fig. 61

Polycyclic xanthone aglycons and associated sugars.

Fig. 62

Paulomycins and associated sugars.

Fig. 63

Phenyl glycosides and associated sugars.

Fig. 64

Oxazole aglycons and associated sugars.

Fig. 65

Porphyrin aglycons and associated sugars.

Fig. 66

Other heterocycle aglycons and associated sugars. Pink fragment highlights differences between tetrapetalones. Red fragment highlights sugar in rubrolone.

Fig. 67

Aglycons with simple moieties and associated sugars.