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Department of Chemistry

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

Responsabilities at Warwick

  • Head of Organic Chemistry Teaching Section

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:

  • Tim Kirkman- 4th year PhD student (EPSRC, with Dr Marcio Dias)- A fragment-based approach for the development of inhibitors of medically relevant dihydrofolate reductases
  • Mohammad Rejaur Rahman- 3rd year PhD student (Commonwealth Scholarship, with Dr Binuraj Menon)-Engineering microbial chemical factories towards integrated chemo-enzymatic catalysis for value added biomolecules
  • Sam Tucker- 2nd year PhD student (Warwick- Monash joint PhD programme, with Prof Max Cryle)-Chemoenzymatic generation of ‘unnatural’ medicinal peptides

  • Esther Fasoyin- 2nd year PhD student (Chancellor's International Scholarship)- Investigation and exploitation of secondary lipid biosynthesis in Rhodococcus bacteria

  • Charles Burgess- 2nd year PhD student (BBSRC-MIBTP)- Novel Chemoenzymatic Approaches to ‘Unnatural’ Products

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

42. Zhang, S.; Zhang, L.; Greule, A.; Tailhades, J.; Marschall, E.; Prasongpholchai, P.; Leng, D. J.; …; Tosin, M.*; Si, T.*; Cryle, M. J.;* ‘P450-mediated dehydrotyrosine formation during WS9326 biosynthesis proceeds via dehydrogenation of a specific acylated dipeptide’, Acta Pharm. Sin. B 2023, in press, https://doi.org/10.1016/j.apsb.2023.03.021.

41. Izore, T.; Ho, Y. T. C.; Kaczmarski, J.; Gavriilidou, A.; Chow, K.; Steer, D.; Goode, R.; Schittenhelm, R.; Tailhades, J.; Tosin, M.; Challis G. L.; Krenske, E.; Ziemert, N.; Jackson, C.; Cryle M. J.; 'Structures of a non-ribosomal peptide synthetase condensation domain suggest the basis of substrate selectivity', Nat. Commun. 2021, 12, 1-14.

40. Leng, D. J. L.; Greule, A.; Cryle, M. J.; Tosin, M. * 'Chemical probes reveal the timing of early chlorination in vancomycin biosynthesis', Chem. Commun. 2021, 57, 2293-96.

39. Izore, T.; Ho, Y. T. C.; Kaczmarski, J.; Gavriilidou, A.; Chow, K.; Steer, D.; Goode, R.; Schittenhelm, R.; Tailhades, J.; Tosin, M.; Challis G. L.; Krenske, E.; Ziemert, N.; Jackson, C.; Cryle M. J.; 'Understanding condensation domain selectivity in non-ribosomal peptide biosynthesis: structural characterization of the acceptor bound state', preprint (Research Square) 2021, DOI: 10.21203/rs.3.rs-125509/v1.

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, 1045–1054.

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.