Coronavirus (Covid-19): Latest updates and information
Skip to main content Skip to navigation

Dr Manuela Tosin

Associate Professor of Organic Chemistry


Development of chemical probes and tools for natural product and chemical biology research

m dot tosin at warwick dot ac dot uk

02476 5 72878

Office C5.05

Manuela Tosin Group

Groups at Warwick


Affiliations


Biography

  • 10/15 – Associate Professor of Organic Chemistry, Warwick

  • 11/10 - 09/15 Assistant Professor of Organic Chemistry, Warwick
  • 11/08 - 09/10 Herchel Smith Fellow, Chemistry, University of Cambridge
  • 11/06 -10/08 Marie Curie Fellow, Chemistry, University of Cambridge
  • 05/05 -10/06 Postdoctoral Researcher, Chemistry, University of Cambridge
  • 05/04 -12/04 Postdoctoral Researcher, Chemistry and Veterinary Biochemistry, University College Dublin
  • 01/01 -12/04 PhD in Chemistry, University College Dublin, Ireland; Royal Irish Academy Prize for Young Chemists 2004 (most outstanding Irish Ph.D. thesis in chemical sciences)
  • 10/94 –09/00 Laurea (Master Degree) in Chemistry cum laude, Università degli Studi di Padova, Padova, Italy

I am working on the following projects at the moment:

  • Chemical probes for the elucidation and the exploitation of different natural product biosynthetic pathways (leading to polyketides, nonribosomal peptides, PUFAs, ...)
  • Investigation of bacterial glycosyltransferases for biocatalysis and biotechnology applications
  • Inhibitors of biological processes associated to disease

Development of chemical probes/tools aiming at:

(i) uncovering the details of complex mechanisms involved in natural product biosynthesis;

(ii) generating novel natural products of improved pharmacological activity;

(iii) exploring new sources of natural products;

(iv) underpinning enzyme function.

Manuela teaches Advanced Medicinal and Biological Chemistry (CH408) and Mechanistic and Biological Chemistry (CH271)


I am supervising the following PhD students:

  • Panward Prasongpholchai- 4th year PhD student (Chancellor's International Scholarship)- Secondary lipid metabolites from marine microorganisms
  • Ryan Packer- 3rd year PhD student- Polyprenyl-dependent glycosylation pathways for natural product and protein functionalisation
  • Scott Andrew- 3rd year PhD student (EPSRC Interdisciplinary DTP)- Investigation of polyprenyl phosphomannose synthases as biocatalysts
  • Heather Scott- 2nd year PhD student (BBSRC-MIBTP)- Functional and structural characterisation of unusual carbohydrate-processing enzymes in natural product biosynthesis
  • Candace Ho- 2nd year PhD student (Monash-Warwick joint PhD programme)- Chemical tools for the characterisation and the exploitation of antibiotic biosynthetic pathways
  • Thays De Souza Carvalho- MRes student- Chemical probing and dissection of iterative polyketide assemblies

If you would like to discuss PhD and Postdoctoral research opportunities at any time please contact me (M.Tosin@warwick.ac.uk).

38. Kilgour, S. L.; Jenkins, R.; Tosin, M.* 'A Photoactivatable Small Molecule Probe for the in vivo Capture of Polyketide Intermediates', Chem. Eur.J. 2019, 25, 16511-16514.

37. Kilgour, S. L.; Kilgour, D. P. A.; Prasongpholchai, P.; O' Connor, P. B. O*.; Tosin, M.* 'A Light-Activated Acyl Carrier Protein 'Trap' for Intermediate Capture in Type II Iterative Polyketide Biocatalysis', Chem. Eur. J. 2019 (VIP article), 25, 16515-16518.

36. Little, R.; Paiva, F.; Jenkins, R.; Hong, H.; Sun, Y.; Demydchuk., Y; Samborskyy, M.; Tosin, M.; Leeper, F.; Dias, M. V. B; Leadlay, P. F. ‘Unexpected Enzyme-catalysed [4+2] Cycloaddition and Rearrangement in Polyether Antibiotic Biosynthesis’, Nat. Catal. 2019, 2, 10451054.

35. Alberti, A.; Leng, D. J.; Wilkening, I.; Song, L.; Tosin, M.; Corre, C. 'Triggering the expression of a silent gene cluster from genetically intractable bacteria results in scleric acid discovery', Chem. Sci. 2019, 10, 453-463.

34. Alberti, A.; Leng, D. J.; Wilkening, I.; Song, L.; Tosin, M.; Corre, C. 'Triggering the expression of a silent gene cluster from genetically intractable bacteria results in scleric acid discovery', bioRxiv 2018, 265645.

33. Ho, Y. T. C.; Leng, D. J.; Ghiringhelli, F.; Wilkening, I.; Bushell, D. P.; Kostner, O.; Riva, E.; Havemann, J.; Passarella, D.; Tosin, M.*; ‘Novel Chemical Probes for the Investigation of Nonribosomal Peptide Assembly’, Chem. Commun. 2017, 53, 7088-7091.

32. Yurkovich, M. E.; Jenkins, R.; Sun, Y.; Tosin, M.;* Leadlay, P. F.;* ’The Polyketide Backbone of Thiolactomycin is Assembled by an Unusual Type I Iterative Synthase’, Chem. Commun. 2017, 53, 2182-2185.

31. Havemann, J.; Yurkovich, M. E.; Jenkins, R.; Harringer, S.; Tao, W.; Wen, S.; Sun, Y.; Leadlay, P. F.; Tosin, M.* ‘Chemical Probing of Thiotetronate Bio-Assembly’, Chem. Commun. 2017, 53, 1912-1915.

30. Wilkening, I.; Gazzola, S.; Riva, E.; Parascandolo, J. S.; Song, L.; Tosin, M.*; 'Second-generation probes for biosynthetic intermediate capture: towards a comprehensive profiling of polyketide assembly', Chem. Commun. 2016, 52, 10392-10395.

29. Parascandolo, J. S.; Havemann, J.; Potter, H. K.; Huang, F.; Riva, E.; Connolly, J.; Wilkening, I.; Song, L.; Leadlay, P. F.; Tosin, M.*; 'Novel insights into 6-methylsalicylic acid bio-assembly via chemical probes', Angew. Chem. Int. Ed. 2016, 55, 3463-3467.

28. Tao, W.; Yurkovich, M. E.; Wen, S.; Lebe, K. B.; Samborskyy, M.; Liu, Y.; Yang, A.; Liu, Y.; Ju, Y.; Deng, Z,; Tosin, M.; Sun, Y.; Leadlay, P. F. 'A Genomics-led Approach to Deciphering the Mechanism of Thiotetronate Antibiotic Biosynthesis', Chem. Sci. 2016, 7, 376-385.

27. Kage, H.; Riva, E.; J. S. Parascandolo, J. S.; Kreutzer, M. F.; Tosin, M.*; Nett, M. * 'Chemical Chain Termination Resolves the Timing of Ketoreduction in a Partially Reducing Iterative Type I Polyketide Synthase', Org. Biomol. Chem. 2015, 13, 11414-11417.

26. Riva, E.; Wilkening, I.; Gazzola, S.; Li, A.; Smith, L.; Leadlay, P. F.; Tosin, M.* 'Chemical Probes for the Functionalization of Polyketide Intermediates', Angew. Chem. Int. Ed. 2014, 53, 11944-11949 (VIP article, highlighted in Nature Chemistry News and Views, February 2015).

25. Wills, R. H.; Tosin, M.; O'Connor, P. B. 'Structural Characterization of Polyketides Using High Mass Accuracy Tandem Mass Spectrometry', Anal. Chem. 2012, 84, 8863–8870.

24. Tosin, M.*; Smith, L.; Leadlay, P. F. ‘Insights into Lasalocid A Ring Formation by Chemical Chain Termination in vivo’, Angew. Chem. Int. Ed. 2011, 50, 11930-11933 (VIP article).

23. Tosin, M.*; Demdychuk, Y.; Parascandolo, J. S.; Blasco Per, C.; Leeper, F. J.; Leadlay, P. F. ‘In vivo Trapping of Polyketide Intermediates from an Assembly Line Synthase using Malonyl-Carba(dethia)-N-Acetyl Cysteamines’, Chem. Commun. 2011, 47, 3460-3462.

22. Kwan, D. H.; Tosin, M.; Schläger, N.; Schulz, F.; Leadlay, P. F. ‘Insights into the Stereospecificity of Ketoreduction in a Modular Polyketide Synthase’, Org. Biomol. Chem. 2011, 9, 2053-2056.

21. Tran, L.; Broadhurst, R. W.; Tosin, M.; Cavalli, A.; Weissman, K. J. ‘Insights into Protein-Protein and Enzyme-Substrate Interactions in Modular Polyketide Synthases’, Chem. Biol. 2010, 17, 705-716.

20. Diaz, M. V. B.; Huang, F.; Chirgardze, D.Y.; Tosin, M.; Spiteller, D.; Dry, E. V. ; Spencer, J.B.; Leadlay, P. F.; Blundell, T. L. ‘Structural Basis for the Activity and Substrate Specificity of Fluoroacetyl-CoA Thioesterase FlK’, J. Biol. Chem. 2010, 85, 22495–22504.

19. Tosin, M.*; Betancor, L.; Stephens, E.; Li, W. M. A.; Spencer, J.B.; Leadlay, P. F. ‘Synthetic Chain Terminators Off-Load Intermediates from a Type I Polyketide Synthase’, ChemBioChem 2010, 11, 539-546.

18. Lazos, O.; Tosin, M.; Slusarczyk, A.; Boakes, S.; Cortés, J.; Sidebottom, P. J.; Leadlay P. F. ‘Biosynthesis of the Putative Siderophore Erythrochelin Requires Unprecedented Cross-Talk between Separate Nonribosomal Peptide Gene Clusters’, Chem. Biol. 2010, 17, 160-173.

17. Sun, Y.; Hahn, F.; Demdychuk, Y.; Chettle, J.; Tosin, M.; Osada, H.; Leadlay, P. F. ‘In vitro Reconstruction of Tetronate RK-682 Biosynthesis’, Nature Chem. Biol. 2010, 6, 99-101.

16. Tosin M.*; Spiteller, D.; Spencer J.B. ‘Malonyl carba(dethia)- and Malonyl oxa(dethia)-coenzyme A as Tools for Trapping Polyketide Intermediates’, ChemBioChem 2009, 10, 1714-1723.

15. Andre, S.; Velasco-Torrijos, T.; Leyden, R.; Gouin, S.; Tosin, M.; Murphy, P.V.; Gabius, H.-J. ‘Phenylenediamine-Based Bivalent Glycophanes: Synthesis and Analysis of the Influence of Scaffold Rigidity and Ligand Spacing on Lectin Binding in Cell Systems with Different Glycomic Profiles’, Org. Biomol. Chem. 2009, 7, 4715-4725.

14. Tran, L.; Tosin, M.; Spencer J.B.; Leadlay, P. F.; Weissman, K. J. Covalent Linkage Mediates Communication between ACP and TE Domains in Modular Polyketide Synthases’, ChemBioChem 2008, 9, 905-915.

13. O'Brien, C.; Polakova, M.; Pitt, N.; Tosin, M.; Murphy, P. V. 'Glycosidation-Anomerisation Reactions of 6,1-Anhydroglucopyranuronic Acid and Anomerisation of b-D-Glucopyranosiduronic Acids Promoted by SnCl4', Chem. Eur. J. 2007, 13, 3, 902-909.

12. Loukou, C.; Tosin, M.; Müller-Bunz, H.; Murphy, P. V. 'Synthesis of Sugar-Lactams from Azides of Glucuronic Acid', Carb. Res. 2007, 342, 12-13, 1953-1959.

11. Cronin, L.; Tosin, M.; Müller-Bunz, H.; Murphy, P. V.‘ The Synthesis of Cyclic Imidates from Amides of Glucuronic Acid and Investigation of Glycosidation Reactions’, Carb. Res. 2007, 342, 1, 111-118.

10. Rawe, S.L.; Zaric, V.; Doyle, D.; Rozas, I.; McMahon, K.; Tosin, M.; Murphy, E.; O’ Boyle, K.M.; Murphy, P.V. 'N-Glycosyl-Thiophene-2-Carboxamides: Synthesis, Structure and Effects on the Growth of Diverse Cell Types', Carb. Res. 2006, 341, 10, 1370-1390.

9. Tosin, M.; Murphy, P.V. 'Synthesis of Scaffolds for Bivalent Ligand Display Based on Glucuronic Acid Anilides. Degree of Amide Isomerism and Scaffold Folding Depends on a Remote Anomeric Group and Configuration', J. Org. Chem. 2005, 70, 4107-17.

8. Tosin, M.; O’ Brien, C.; Fitzpatrick, G.M.; Müller-Bunz, H.; Glass, W.K.; Murphy, P.V. 'Synthesis and Structural Analysis of Anilides of Glucuronic Acid and Relevance for Display of Aromatic Groups on Carbohydrate Scaffolding', J. Org. Chem. 2005, 70, 4096-106.

7. Tosin, M.; Gouin, S.; Murphy, P.V. 'Synthesis of Structurally Diverse and Defined Bivalent Mannosides on Saccharide Scaffolding', Org. Lett. 2005, 7, 211-14.

6. Tosin, M.; Müller-Bunz, H.; Murphy, P.V. 'Synthesis and X-ray Single Crystal Structure of a Novel Bivalent Glycocluster', Chem. Commun. 2004, 494-95.

5. Poláková, M.; Pitt, N.; Tosin, M.; Murphy, P.V. ‘Glycosidation Reactions of Silyl Ethers with Conformationally Inverted Donors Derived from Glucuronic Acid. Stereoselective Glycoside and 2-Deoxyglycoside Synthesis', Angew. Chem. Int. Ed. 2004, 43, 2518-21.

4. Murphy, P.V.; Bradley, H.; Tosin, M.; Pitt, N.; Fitzpatrick, G.M.; Glass, W.K. 'Development of Carbohydrate Based Scaffolds for Restricted Presentation of Recognition Groups. Extension to Divalent Ligands and Implications for the Structure of Dimerized Receptors', J. Org. Chem. 2003, 68, 5693-5704.

3. Tosin, M.; Murphy, P.V. 'Synthesis of a-Glucuronic Acid and Amide Derivatives in the Presence of a Participating 2-Acyl Protecting Group', Org. Lett. 2002, 4, 3675-78.

2. Enright, P.M.; Tosin, M.; Nieuwenhuyzen, M.; Cronin, L.; Murphy, P.V. 'A Study of the Epoxidation of 6-Deoxyhex-5-enopyranosides. 1,5-Dicarbonyl Derivatives and Novel Synthetic Routes to D-xylo-Hexos-5-ulose and D-lyxo-Hexos-5-ulose', J. Org. Chem. 2002, 67, 3733-41.

1. O’ Brien, J. L.; Tosin, M.; Murphy, P.V. 'Novel Synthesis of the Glycosidase Inhibitor Deoxymannojirimycin and of a Synthetic Precursor D-lyxo-hexos-5-ulose', Org. Lett. 2001, 3, 3353-56.