Mishtu Dey

Mishtu Dey
Assistant Professor
W285 CB
  • M.S., M.Phil, Utkal University, India (1998)
  • Ph.D., Indian Institute of Technology Bombay (2005)
  • Postdoctoral Fellow, University of Nebraska-Lincoln and University of Michigan (2005-2008)
  • Howard Hughes Medical Institute Postdoctoral Research Associate, Massachusetts Institute of Technology (2008-2011)

Metallobiochemistry; biochemical, spectroscopic, and X-ray crystallographic studies; catalytic mechanisms of redox-active enzymes; Ni and methane biocatalysis; catabolism of organosulfur compound by marine microbes; post-translational modifications of metalloproteins; metal ions and mammalian oxygen sensing pathway.

Research Interests: 

Research in our laboratory resides at the interface of chemistry and biology to understand the molecular mechanisms of metalloenzymes important for bioenergy conversion, human health and disease, or environmentally valuable. The focus is on applying a combination of enzymology, microbiology, molecular biology, and X-ray crystallographic technique to investigate the catalytic mechanisms of redox-active metalloenzymes. Our research is highly interdisciplinary, drawing from synthetic chemistry, protein biochemistry, biophysics, and microbial bioprocessing.

Methanogenesis. Methane, the principal component of natural gas is produced biologically by a group of microbes called methanogens. Approximately one billion tons of methane is generated every year by microbial activity and serves as a valuable source of renewable energy. Methane biogenesis is catalyzed by the nickel-containing enzyme methyl coenzyme M reductase, which contains unique amino acid modifications near the active site and we are interested in the biosynthesis of these rare post-translational modifications.

Organosulfur metabolismThe volatile organic sulfur compound dimethylsulfide (DMS) is produced in marine environments by bacterial degradation of dimethylsulfoniopropionate (DMSP). About thousands of tons of DMS is released to the atmosphere every year and it’s acidic oxidation products initiate cloud nucleation. The pathways for DMSP degradation involve enzymatic cleavage to simpler sulfur compounds that are important metabolites for marine bacteria and play significant role in global sulfur and carbon cycles. We study the mechanism of enzymatic degradation of bioactive marine metabolites.

Mammalian oxygen sensing pathwayThe response to oxygen in mammals is regulated by hypoxia-inducible factor (HIF), a key transcription factor that senses oxygen. Under normal oxygen conditions, iron enzymes hydroxylate HIF and promote degradation. With limiting oxygen, hydroxylation of HIF is diminished thereby stimulating the transcription of hypoxia target genes. Defects in crucial oxygen sensing proteins result in defects in erythropoiesis, angiogenesis, cell proliferation, and apoptosis. Our focus is directed towards understanding various aspects of mammalian oxygen sensing at a molecular level."

Recent Publications: 
  • Yun, D.; Dey, M.; Higgins, L.J.; Yan, F.; Liu, H.-W.; Drennan, C.L.  Structural Insights into the mechanism of Regioselectivity of Hydroxypropylphosphonic Acid Epoxidase.  J. Am. Chem. Soc., 2011, 133, 11262-9.
  • Cedervall, P.E.; Dey, M.; Li, X.; Sarangi, R.; Hedman, B.; Ragsdale, S.W.; Wilmot, C.M.  Structural analysis of a Ni-methyl species in methyl-coenzyme M reductase from Methanothemobacter marburgensis. J. Am. Chem. Soc2011 133, 5626-8. (Faculty of 1000 pick).
  • Dey, M.; Li, X.; Kunz, R.C.; Ragsdale, S.W.  Organometallic and Radical Intermediates in the Catalytic Mechanism of Methyl-Coenzyme M Reductase using the natural substrate methyl-coenzyme M and a Coenzyme B substrate analog.  Biochemistry 2010, 28, 49, 10902-11.
  • Dey, M.; Li, X.; Zhou, Y.; Ragsdale, S.W.  Evidence for Organometallic Intermediates in Bacterial Methane Formation Involving the Nickel Coenzyme F430Met Ions Life Sci. 2010 7, 71-110.
  • Cedervall, P.E.;# Dey, M.;# Pearson, A.R.; Ragsdale,S.W.; Wilmot, C.M.  Structural Insight into Methyl-Coenzyme M Reductase Chemistry using Coenzyme B Analogues.  Biochemistry 2010, 49, 7683-93 (# indicates equal contribution).
  • Dey, M.; Kunz, R.C.; Lyons, D.M.; Ragsdale, S.W.  Characterization of alkyl-nickel adducts generated by reaction of methyl-coenzyme m reductase with brominated acids.  Biochemistry 2007, 46, 11969-78.
  • Dey, M.; Telser, J.; Kunz, R.C.; Lees, N.S.; Ragsdale, S.W.; Hoffman, B.M.  Biochemical and spectroscopic studies of the electronic structure and reactivity of a methyl-Ni species formed on methyl-coenzyme M reductase.  J. Am. Chem. Soc2007, 129, 11030-2. (Faculty of 1000 Pick).
  • Dey, M.; Kunz, R.C.; Van Heuvelen, K.M.; Craft, J.L.; Horng, Y.-C.; Tang, Q.; Bocian, D.F.; George, S.J.; Brunold, T.C.; Ragsdale, S.W.  Spectroscopic and Computational Studies of Reduction of the Metal versus the Tetrapyrrole Ring of Coenzyme F430 from Methyl-Coenzyme M Reductase.  Biochemistry, 2006, 45, 11915-33.
  • Dey, M.; Rao, C.P.; Guionneau, P.  Structural characterization and reactivity of Cu(II) complex of p-tert-butyl-calix[4]arene bearing two imine pendants at lower rim. Inorg. Chem. Commun. 2005, 8, 998-1001.
  • Dey, M.; Rao, C.P.; Saarenketo, P.K.; Rissanen, K.; Kolehmainen, E.; Guionneau, P.; “Mn(IV) and Co(III)-complexes of -OH-rich ligands possessing O2N, O3N and O4N cores: Syntheses, Characterization and Crystal Structures.  Polyhedron 2003, 22, 3515-3521.