Dr Manuela Tosin

Manuela Tosin

Associate Professor

M.Tosin@warwick.ac.uk
+44 (0)2476 5 72878
Tosin GroupLink opens in a new window

About Me

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

Groups at Warwick

Manuela Tosin Group

Responsibilities at Warwick

Y4 Lead

Affiliations

RSC Chemical Biology and Bioorganic Group

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

Current projects

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

Research interests Publications

46. Kirkman, T.; Sketcher, A.; de Morais Barroso, V.; Ishida, K.; Tosin, M.; Dias, M. B. V. ‘Crystal Structure of Dihydrofolate Reductase from the Emerging Pathogenic Fungi Candida auris’, Acta Crystallogr. D 2023, doi.org/10.1107/S2059798323004709.

45. Ho, Y. T. C.; Kaczmarski, J. A.; …; Tosin, M.; Jackson, C. J.; Cryle, M. J. ‘Not Such an Innocent Bystander: the Impact of Stabilised Phosphopantetheine Moieties on NRPS Biosynthesis’, Chem. Commun. 2023, doi.org/10.1039/D3CC01578E.

44. Ho, Y. T. C.; Izore, T.;. ..; Tosin, M.; Jackson, C. J.; Cryle, M. J. ‘Exploring the Selectivity and Engineering Potential of an NRPS Condensation Domain Involved in the Biosynthesis of the Thermophilic Siderophore Fuscachelin’, Front. Cat. 2023, doi: 10.3389/fctls.2023.1184959.

43. Kirkman, T.; Tan, S. F.; Chavez-Pacheco, S. M.; Hammer, A.; Abell, C.; Tosin, M.; Coyne, A.; Dias, M. B. V. ‘Fragment Merging Strategies with Known Pyrimidine Scaffolds Targeting Dihydrofolate Reductase from Mycobacterium tuberculosis,’ ChemMedChem 2023, doi.org/10.1002/cmdc.202300240.

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, 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.

Teaching and supervision

Manuela teaches Advanced Medicinal and Biological Chemistry (CH408), Mechanistic and Biological Chemistry (CH271), Selective Organic Synthesis (CH270) and acts as MChem project coordinator (CH401).

I am supervising the following PhD students:

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- 3rd year PhD student (Warwick- Monash joint PhD programme, with Prof Max Cryle)-Chemoenzymatic generation of ‘unnatural’ medicinal peptides
Esther Fasoyin- 3rd year PhD student (Chancellor's International Scholarship)- Investigation and exploitation of secondary lipid biosynthesis in Rhodococcus bacteria
Charles Burgess-3rd 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).