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A Comprehensive Review of Glycosylated Bacterial Natural Products

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A Comprehensive Review of Glycosylated Bacterial Natural Products Chemical Society Reviews A comprehensive review of glycosylated bacterial natural products Journal: Chemical Society Reviews Manuscript ID: CS-REV-11-2014-000426.R1 Article Type: Review Article Date Submitted by the Author: 26-Nov-2014 Complete List of Authors: Elshahawi, Sherif; University of Kentucky, Shaaban, Khaled; University of Kentucky, Kharel, Madan; University of Maryland Eastern Shore, School of Pharmacy and Health Profession Thorson, Jon; University of Kentucky, Pharmacy Page 1 of 186 Chemical Society Reviews A comprehensive review of glycosylated bacterial natural products Sherif I. Elshahawi,*ab Khaled A. Shaaban,*ab Madan K. Kharelc and Jon S. Thorson†ab a Department of Pharmaceutical Sciences, College of Pharmacy, University of Kentucky, Lexington, KY, USA; b Center for Pharmaceutical Research and Innovation, College of Pharmacy, University of Kentucky, Lexington, KY, USA; c School of Pharmacy, University of Maryland Eastern Shore, Princess Anne, Maryland, USA * Sherif I. Elshahawi and Khaled A. Shaaban have contributed equally to this work. † Corresponding Author, Email: [email protected]. Covering all the glycosylated bacterial natural products through 2012 and some of 2013 Chemical Society Reviews Page 2 of 186 1. Introduction 2. Aminoglycosides 2.1. Pactamycins 2.2. Other members 3. Angucyclines 3.1. Tetrangomycin-Type (Landomycins) 3.2. Aquayamycin-Type (Saquayamycin and Urdamycin Analogs) 3.3. Other Related Aquayamycin-type Angucyclines 3.4. Jadomycin and Gilvocarcin-Types (Jadomycins, Ravidomycins, Chrysomycins and Gilvocarcin) 4. Anthracyclines, Tetracyclines, Quinones and Tricyclines 4.1. Anthracyclines 4.2. Hibarimicins 4.3. Tetracycline-type Antibiotics 4.4. Aureolic Acids and Related Tetracyclines 4.5. Pyranonaphthoquinones 4.6. Benzoquinones Related Antibiotics 5. Benanomicins and Pradimicins 6. Chartarin-analogs 7. Coumarins 8. Enediynes 8.1. 9-membered Enediynes 8.2. 10-membered Enediynes 9. Flavonoids and Isoflavonoids 10. Indoles and Indolocarbazoles 10.1. Fused indoles 10.2. Simple Indoles 11. Lipids, Polyenes and Carotenoids 12. Macrolides and Macrolactams 12.1. 12-Membered Macrolides 12.2. 14-Membered Macrolides 12.3. 16-Membered Macrolides 12.4. 18-Membered Macrolides 12.5. 20-Membered Macrolides 12.6. 22-Membered Macrolactones 12.7. 24-Membered Macrolactones 12.8. Macrodiolides 12.9. Super Macrolactones (ring size 32-48) 12.10. Polyene Macrolides 12.11. Macrolactams and Related Glycosylated Metabolites 12.12. Spirotetronates 12.13. Spinosyns 13. Nucleosides and Nucleoside-Derived Compounds 13.1. Pyrimidine-Derived Nucleosides 13.1.1 Uracil-Derived Nucleosides Page 3 of 186 Chemical Society Reviews 13.1.2 Cytosine-Derived Nucleosides 13.2 Purine-Derived Nucleosides 13.2.1. Adenine-Derived Nucleosides 13.2.2. Guanine and Other Miscellaneous Nucleosides 14. Orthoesters 14.1. Orsellinic Acid Derivatives 14.2. Aminocyclitol Derivatives 15. Peptides 15.1. Bleomycins 15.2. Vancomycins 15.3. Mannopeptimycins 15.4. Salmochelins and Salmycins 15.5. Lincosamides 15.6. Thiazoles 15.7. Lipoglycopeptides 15.8. Miscellaneous Anti-infective Peptides 15.9. Other Peptides 16. Phenazines 17. Piericidins and Pyranones 18. Pluramycins 19. Polyethers 20. Pterins 21. Streptothricins 22. Terpenes and Sterols 22.1. Sesquiterpenes and Diterpenes 22.2. Triterpenes 23. Miscellaneous 23.1. Trioxacarcin Analogs 23.2. Polycyclic Xanthones and Related Analogs 23.3. Paulomycin Related Compounds 23.4. Phenyls and Related Compounds 23.5. Heterocycles 23.5.1. Oxazoles 23.5.2. Porphyrins 23.5.3. Other Heterocycles 23.6. Additional Simple Aglycons 24. Conclusions Chemical Society Reviews Page 4 of 186 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 3,426 glycosides containing 344 distinct appended carbohydrates and highlights a range of unique opportunities for future biosynthetic study and glycodiversification efforts. TOC GRAPHIC: A compilation of the rich diversity of bacterial secondary metabolite glycosides. Keywords aminoglycosides, angucyclines, anthracyclines, benanomicins, carbohydrates, chartarins, coumarins, enediynes, flavonoids, glycosyltransferases, indoles, indolocarbazoles, lipids, macrolactams, macrolides, nucleosides, orthoesters, paulomycins, peptides, phenazines, piericidins, pluramycins, polyenes, polyethers, polyketides, porphyrins, pradimicins, pterins, saccharides, secondary metabolites, streptothricins, sugars, terpenes, tetracyclines, trioxacarcins, xanthones Page 5 of 186 Chemical Society Reviews Biosketch Sherif Elshahawi received his B.S. degree in Pharmaceutical Sciences (2000) from Cairo University, a Master’s degree in Pharmacognosy (2006) from the University of Mississippi and a Ph.D. degree in Biochemistry and Molecular Biology (2012) from the School of Medicine at Oregon Health & Science University with Professor Margo Haygood. He is currently a postdoctoral scholar in the Center for Pharmaceutical Research and Innovation at University of Kentucky College of Pharmacy. Dr. Elshahawi’s research interests include the isolation and phylogenetic analyses of microorganisms from unusual environments and the biosynthesis, isolation, bioassay and resistance of bioactive secondary metabolites. Dr. Khaled A. Shaaban obtained his B.S. degree in Chemistry (2000) from Mansoura University (Egypt) and M.S. (2005) and PhD. degrees in Organic Chemistry (2009) from the University of Göttingen (Germany) with Professor Hartmut Laatsch. He subsequently held postdoctoral appointments at the University of Kentucky (Professor Jürgen Rohr, 2009-2011) and The Scripps Research Institute (TSRI Florida, Professor Ben Shen, 2011-2012) prior to joining the Center for Pharmaceutical Research and Innovation at University of Kentucky College of Pharmacy as a Research Scientist. His major research interests include isolation of bacterial strains, screening, scale-up fermentation, isolation and structure elucidation of novel bioactive microbial natural products. Chemical Society Reviews Page 6 of 186 Dr. Kharel obtained his B.S. (1998) and M.S. (2000) from the Tribhuvan University (Nepal), a Ph.D. in biochemistry from the Sun Moon University (South Korea, 2007) and a Ph.D. in pharmaceutical sciences from the University of Kentucky (2010, Professor Jürgen Rohr). Dr. Kharel served as a research faculty in the University of Kentucky Center for Pharmaceutical Research and Innovation (2012-2013) and currently is an Assistant Professor of Medicinal Chemistry, Department of Pharmaceutical Sciences, University of Maryland Eastern Shore. His research interests include elucidation of function of novel enzymes, enzymatic synthesis of natural products, and isolation of new bioactive microbial natural products. Jon received his B.A. from Augsburg College (1986), a Ph.D. from the University of Minnesota (1993, Professor Hung-wen Liu) and was a Helen Hay Whitney postdoctoral fellow at the University of California, Berkeley (1993-1996, Professor Peter Schultz). He has served on the faculty of the Memorial Sloan-Kettering Cancer Center and the Sloan-Kettering Division, Joan and Sanford I. Weill Graduate School of Medical Sciences, Cornell University (1996-2001), the University of Wisconsin - Madison School of Pharmacy (2001-2011), and the University of Kentucky College of Pharmacy (2011-present) where he is also the director of the Center for Pharmaceutical Research and Innovation. His research interests include bioprospecting, biocatalysis and biosynthesis. Page 7 of 186 Chemical Society Reviews 1. Introduction While it is well-established that the glycosylation of naturally-occurring and/or synthetic small molecule-based drugs can dramatically influence the pharmacological properties of the parent scaffold,1-17 there remains a lack of accuracy regarding the prevalence and/or extent of glycosidic diversity in the context of naturally-occuring glycosides. The current review attempts to address this gap of knowledge by providing a systematic analysis of all naturally-occurring glycosylated bacterial secondary metabolites reported in the scientific literature. AntiBase 201218 served as a key resource for glycoside identification and all glycosides were structurally validated via an analysis of the primary literature and corrected where necessary prior to integration into this compilation. Based upon an analysis of 15,940 bacterial natural products, over one fifth (3,426 compounds, 21.5%, Figure 1A) are glycosides wherein glycosylated macrolides and macrolactams represent the largest allocation (738 compounds, 21.5% of all bacterial glycosides, Figure 1B). Further analysis of the range of saccharides represented across all 3,426 bacterial glycosides revealed 344 distinct carbohydrates (Figure 1C and Table 1). For this latter consideration, carbohydrates were only designated as ‘distinct’ based upon differences within the fundamental monsaccharide core (specifically, notable stereochemical and/or functional group variation, including anomeric configuration) whereas simple modifications of a given common sugar core (e.g., O/N/S- alkyl/acyl substitutions) were designated as identical to the parental core saccharide. The content of this comprehensive review has been organized based upon aglycon class/structure as indicated in Figure 1B wherein each section provides additional relevant information pertaining to the glycosides represented within
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