E. Neil G. Marsh

Professor of Chemistry

Ph.D., University of Cambridge
Postdoctoral Fellow, Johns Hopkins University

Research Focus: Enzyme Mechanism and Structure; Protein Design

Phone: 734.763.6096
E-mail: nmarsh@umich.edu
Fax: 734.764.8815

My laboratory is interested in enzyme mechanisms, the structure and function of bioactive peptides and self-assembling proteins. Current projects include:  enzymes involved in hydrocarbon metabolism, that could be useful for biofuel production; using fluorinated amino acids to modify the properties of biologically-active peptides and study their mechanism of action; developing strategies for the assembly of proteins into nano-cages.  Our research is inherently inter-disciplinary and draws on a synergistic combination of bio-organic, bio-inorganic and bio-physical chemistry.  We are fortunate to enjoy various productive collaborations with other research groups at Michigan.

Enzymes for new biofuels production
The design of high efficiency, environmentally benign methods for producing biofuels will require engineering new metabolic pathways, which, in turn, requires new enzymes.  We are studying several enzymes involved in hydrocarbon metabolism from various organisms.  These enzymes typically catalyze chemically difficult reactions that involve either converting fatty acids to hydrocarbons or functionalizing aromatic hydrocarbons to make them less toxic.  In many cases the enzymes contain metals and the reactions may involve the formation of novel organometallic complexes and/or the formation of free radicals.  Despite their potentially useful applications, these enzymes are poorly understood in terms of their catalytic properties, which hinders attempts to engineer them into new biochemical pathways.  We are using a variety of techniques to study the mechanisms of these enzymes and engineer them towards new substrate specificities.

Fluorinated peptides and “Teflon” proteins
Fluorine is a remarkably useful element for studying biology because it is easily substituted for hydrogen and has excellent NMR properties.  De-novo designed “Teflon” proteins incorporating highly fluorinated amino acids in their hydrophobic cores exhibit useful new properties such as increased thermal stability, resistance to unfolding in organic solvents, and resistance to degradation by proteases.  We using a variety of techniques, in particular 19F NMR, to understand how fluorination alters the structure and dynamics of these proteins and thereby gives rise to these useful properties.  We are also using 19F NMR to study the interactions and dynamics of bio-active peptides, including peptides involved the innate immune system and amyloid formation.  The sensitivity of the fluorine nucleus to chemical environment and peptide dynamics makes 19F NMR an excellent tool for detecting transient intermediates in amyloid formation.

Self-assembling protein nano-cages
The assembly of individual protein subunits into higher order (quaternary) structures is a ubiquitous feature of biology and essential for the biological function of many proteins.  The remarkable diversity of structural and functional properties exhibited by proteins suggests that developing approaches for assembling proteins into new, large-scale supramolecular structures will provide a powerful approach for the construction of novel, responsive biomaterials.  We are developing a novel symmetry-based approach to assemble proteins into nano-cages with defined geometries and stoichiometries that is independent of the structural details of the protein fold.  One important application for these protein nano-cages is to purpose them as a nanoparticle scaffolds to deliver imaging agents or therapeutics to specific, ligand-targeted cells.  Protein nano-cages are expected to have many advantages over other nanoparticle scaffolds, which can be toxic, immunogenic, or variable with respect to the number of ligands carried on the scaffold.

Marsh Research Group



Research Fellow of the Royal Society
Fellow of the Royal Society of Chemistry
Sc.D., University of Cambridge


Representative Publications

  1. B. Khara, N. Menon, C. Levy, D. Mansell, D. Das., E. N. G. Marsh, D. Leys and N. S. Scrutton (2013). Production of Propane and Other Short Chain Alkanes by Structure-based Engineering of Ligand Specificity in Aldehyde Decarbonylase. ChemBioChem, in press

  2. Y. Suzuki, J.R. Brender, M. Soper, J. Krishnamoorthy, Y. Zhou, N. Kotov, B. Ruotolo, A. Ramamoorthy and E.N.G. Marsh (2013). “Resolution of oligomeric species during the aggregation of Aβ1-40 using 19F NMR”. Biochemistry, 52, 1903 -1912

  3. B.C. Buer, B.L. Levin and E.N.G. Marsh (2013). “Perfluoro-tert-butyl-homoserine as a sensitive 19F NMR reporter for peptide-membrane interactions in solution”. J. Peptide Sci., 19, 308 - 314

  4. B. Paul, D. Das, B. Ellington and E.N.G. Marsh (2013). “The reaction of cyclopropyl aldehydes with cyanobacterial aldehyde decarbonylase”. J. Am. Chem. Soc, 135, 5234 -5237

  5. B.C. Buer, J.L. Meagher, J.A. Stuckey and E.N.G. Marsh (2012). “Structural Basis for the Enhanced Stability of Highly Fluorinated Proteins”. Proc. Natl. Acad. Sci. USA, 109, 4810 - 4815

  6. B.C. Buer and E.N.G. Marsh (2012). “Fluorine: a new element in protein design”. Protein Science, 21 453 - 462

  7. G.D. Román Meléndez and E.N.G. Marsh (2012). “Adenosylcobalamin enzymes:  theory and experiment begin to converge”. Biochem. Biophys. Acta, 1824, 1154 - 1164

  8. B.C. Buer, B.L. Levin and E.N.G. Marsh (2012). “Origin of the thermodynamic stability associated with highly fluorinated proteins”. J. Am. Chem. Soc, 134, 13027 - 13034

  9. Y. Suzuki, J.R. Brender, K. Hartman, A. Ramamoorthy and E.N.G. Marsh (2012). “Alternative Pathways of Human Islet Amyloid Polypeptide Aggregation Distinguished by 19F NMR-Detected Kinetics of Monomer Consumption”. Biochemistry, 41, 8154 -8162

  10. D.P. Patterson, A.M. Desai, M.M. Banaszak Holl and E.N.G. Marsh (2011). “Evaluation of a symmetry-based strategy for assembling protein complexes”. RSC Advances, 1 1004 -1012