Dennis R. Dean

Program Focus

Research in the laboratory of Dennis Dean is focused on two principal themes: the mechanism for biological nitrogen fixation and the biological pathways for assembly of simple and complex metalloclusters.  With respect to nitrogen fixation, our group developed a combined biochemical-genetic approach to identify where substrates interact with nitrogenase, the biological catalyst of nitrogen fixation.  This work enabled a series of biophysical approaches leading to the development of a comprehensive model for how certain substrates interact with the nitrogenase active site.

Very recently our laboratory, in collaboration with Lance Seefeldt at Utah State University, used a genetic approach to remodel nitrogenase such that it has the capacity to reduce carbon dioxide to yield methane and various short-chain high-value olefins.  This finding suggests that the nitrogenase mechanism could provide clues for the rational development of metal-based catalysts for carbon dioxide sequestration.

The second theme has involved investigations on the biological assembly of iron-sulfur clusters.  These simple inorganic structures are perhaps nature’s most ancient prosthetic group and are likely to have contributed to the emergence of life on earth.  Our laboratory discovered the biological mechanism for the assembly of iron-sulfur clusters and introduced the concept that both simple and complex iron-sulfur-containing prosthetic groups are pre-assembled on molecular scaffolds. Both in vitro and in vivo approaches have been used to establish the validity of the scaffold hypothesis.  Both the mechanism of sulfur trafficking and the role of scaffolds in metallocluster assembly have now been established as nearly universal biological processes.  Recent progress in this area has involved a collaborative project with Juan Fontecilla’s group in Grenoble to elucidate the crystallographic structure of an iron-sulfur cluster biosynthetic complex captured in the process of cluster assembly.  Ongoing work involves a comprehensive whole-genome transcriptome analysis of bacterial strains that are defective in various aspects of iron-sulfur assembly with the goal of understanding how this process is integrated with and contributes to intermediary metabolism.

Current Projects

• 4/1/09-3/31/14: National Institutes of Health (GM59087).  “Nitrogenase Mechanism”, PI:  Lance Seefeldt, Co-PI:  Dennis R. Dean
• 6/1/09-5/31/14 : National Science Foundation (STEM 085198). “Broadening opportunities for non-traditional graduate students in biomolecular science”, PI:  Dennis R. Dean, Co-PI:  Carlyle Brewster
• 7/1/13-6/30/16: Department of Energy. “Nitrogenase reduction of CO₂ to hydrocarbons”, PI:  Lance Seefeldt, C0-PI: Dennis R. Dean

Dr. Dean's PubMed Site

Dr. Dean's Google Scholar Site

Danyal K, Shaw S, Page TR, Duval S, Horitani M, Marts AR, Lukoyanov D, Dean DR, Raugei S, Hoffman BM, Seefeldt LC, Antony E. “Negative cooperativity in the nitrogenase Fe protein electron delivery cycle.”  Proc Natl Acad Sci U S A. 113(40): (2016):E5783-E5791.

Fixen KR, Zheng Y, Harris DF, Shaw S, Yang ZY, Dean DR, Seefeldt LC, Harwood CS. “Light-driven carbon dioxide reduction to methane by nitrogenase in a photosynthetic bacterium.”  Proc Natl Acad Sci U S A. 113(36): (2016):10163-7.

Yang ZY, Ledbetter R, Shaw S, Pence N, Tokmina-Lukaszewska M, Eilers B, Guo Q, Pokhrel N, Cash VL, Dean DR, Antony E, Bothner B, Peters JW, Seefeldt LC.  “Evidence That the Pi Release Event Is the Rate-Limiting Step in the Nitrogenase Catalytic Cycle.”  Biochemistry.55(26):3625-35.(2016).

Hoffman B.M., Lukoyanov D., Dean D.R., Seefeldt L.C. "Nitrogenase: A Draft Mechanism.". Acc Chem Res 46(2): (2013): 587-95.

Seefeldt L.C., Yang Z.Y., Duval S., Dean D.R. "Nitrogenase Reduction of Carbon-Containing Compounds.". Biochim Biophys Acta Aug-Sep;1827(8-9): (2013): 1102-11.

Yamanaka Y., Zeppieri L., Nicolet Y., Marinoni E.N., de Oliveira J.S., Odaka M., Dean D.R., Fontecilla-Camps J.C. "Crystal Structure and Functional Studies of an Unusual L-Cysteine Desulfurase from Archaeoglobus Fulgidus.". Dalton Trans. 42(9): (2013): 3092-

Liu Y, Dos Santos P.C., Zhu X., Orlando R., Dean D.R., Söll D, Yuan J. "Catalytic Mechanism of Sep-Trna:Cys-Trna Synthase: Sulfur Transfer Is Mediated by Disulfide and Persulfide.". J Biol Chem. Feb 17;287(8): (2012): 5426-33.

Fee T.J., Dean D.R., Eberhardt A.W., Berry J.L. "A Novel Device to Quantify the Mechanical Properties of Electrospun Nanofibers.". J Biomech Eng 134(10): (2012): 104503.

George S.J., Barney B.M., Mitra D., Igarashi R.Y., Guo Y, Dean D.R., Cramer S.P., Seefeldt L.C. "Exafs and Nrvs Reveal a Conformational Distortion of the Femo-Cofactor in the Mofe Nitrogenase Propargyl Alcohol Complex.". J Inorg Biochem 112 (2012): 85-92.

Mayweather D., Danyal K., Dean D.R., Seefeldt L.C., Hoffman BM. "Correction to Temperature Invariance of the Nitrogenase Electron Transfer Mechanism.". Biochemistry. 51(44 (2012): 9027.

Mayweather D., Danyal K., Dean D.R., Seefeldt L.C., Hoffman B.M. "Temperature Invariance of the Nitrogenase Electron Transfer Mechanism.". Biochemistry 51(42 (2012): 8391-8.

Yang Z.Y, Moure V.R., Dean D.R., Seefeldt L.C. "Carbon Dioxide Reduction to Methane and Coupling with Acetylene to Form Propylene Catalyzed by Remodeled Nitrogenase.". Proc Natl Acad Sci U S A 109(48): (2012): 19644-8.

E. N. Marinoni,  J.S de Oliveira, Y. Nicolter,  E. C. Raulfs, P. Amara, D. R. Dean, and J. C. Fontecilla- Camps. (IscS-IscU)2 complex structure provide mechanistic insights of Fe2S2 biogenesis and transfer. Angewandte Chemie. 2012.

Lukoyanov D., Yang Z.Y., Barney B.M., Dean D.R., Seefeldt L.C.,  Hoffman B.M. Unification of reaction pathway and kinetic scheme for N2 reduction catalyzed by nitrogenase. Proc Natl Acad Sci .USA. 2012.

Seefeldt L. C., Hoffman B.M., and Dean D.R. Electron transfer in nitrogenase catalysis. Curr Opin Chem Biol.. 2012.

Danyal K, Dean D. R., Hoffman B. M., and L. C. Seefeldt. Electron transfer within nitrogenase: Evidence for a ‘deficit-spending’ mechanism. Biochemistry. 2011;50:9255–9263.

Doan P.E., Telser J., Barney B. M., Igarashi R. Y., Dean D. R., Seefeldt L. C., and B. M. Hoffman. 57Fe ENDOR spectroscopy and ‘electron inventory’ analysis indicate that nitrogenase FeMo-cofactor cycles through only two redox states. J. Am. Chem. Soc.. 2011;133:17329–17340.

Dos Santos P.C and D.R Dean. Coordination and fine-tuning of nitrogen fixation in Azotobacter vinelandii. Molec Microbiol. 2011;79:1132–1135.

Hamilton T.L .,Jacobson M., Ludwig M., Boyd E. S., Bryant D. A., Dean D. R., and J. W. Peters. Differential accumulation of nif structural gene mRNA in Azotobacter vinelandii. J. Bacteriol.. 2011;193:4534–4536.

Hamilton T.L, Ludwig M., Dixon R. Boyd, Dos Santos, P. C., Setubal J., Bryant D. A., Dean D. R., and J. W. Peters. Transcriptional profiling of nitrogen fixation in Azotobacter vinelandii. J. Bacteriol.. 2011;193:4477–4486.

Liu Y, Dos Santos P. C., Zhu X., Orlando R., Dean D. R., Soll D., and J. Yuan. The catalytic mechanism of sep-tRNA: Cys-tRNA synthase: sulfur transfer is mediated by disulfide and persulfide. J. Biol. Chem.. 2011.

Lukoyanov D, Dikanov S. A., Yang Z-Y., Barney B. M., Samoilova R. I., Narasimhulu K. V., Dean D. R., Seefeldt L. C., and B. M. Hoffman. ENDOR/HYSCORE Studies of the Common Intermediate Trapped during Nitrogenase Reduction of N2H2, CH3N2H, and N2H4 Support an alternating reaction pathway for N2 reduction. J. Am. Chem. Soc.. 2011;133:11655–11664.

Yang Z-Y, Dean D. R., and L. C. Seefeldt. Molybdenym nitrogenase catalyzes the reduction and coupling of CO to form hydrocarbons. J. Biol. Chem.. 2011;286:19417–19421.

Danyal K D., Mayweather D., Dean D.R., Seefeldt  L. C., and B. M. Hoffman. Conformational gating of electron transfer from the nitrogenase Fe protein to MoFe protein. J. Am. Chem. Soc.. 2010:6894–6896.

Danyal K, Inglet B., Vincent K. A., Barney B. M., Hoffman B. M., Armstrong F. A., Dean D. R. and Seefeldt L. C. Uncoupling nitrogenase: Catalytic reduction of hydrazine to ammonia by a MoFe protein in the absence of Fe protein-ATP. J. Am. Chem. Soc.. 2010;132:13197–13199.

Dos Santos P.C., and Dean DR. Electrons in Fe-S protein assembly. Nature Chem. Biol.. 2010;6:700–701.

Lukoyanov D Z., Y. Yang, D. R. Dean, L. C. Seefeldt ,and B. M. Hoffman. Is Mo involved in hydride binding of the four-electron reduced (E4) intermediate of the nitrogenase MoFe protein? J. Am. Chem. Soc.. 2010;132:2526–2528.

Sarma RBMB,  S. Keable, D. R. Dean, and J. W. Peters. Insights into substrate binding at FeMo-cofactor in nitrogenase from the structure of an alpha 70 Ile MoFe protein. J. Inorg. Biochem.. 2010;104:385–389.

Yang Z -Y., Seefeldt L. C., Dean D. R., Cramer S. P. ,and S. J. George. Steric control of the Hi-CO MoFe nitrogenase complex revealed by stopped-flow infra-red spectroscopy. Angew. Chemie. 2010;50:272–275.

Barney B. M., DL R. Y.Igarashi, M. Laryukhin, T.C Yang, D. R. Dean, B. M. Hoffman, L. C. Seefeldt. Trapping an intermediate of dinitrogen (N2) reduction on nitrogenase. Biochemistry. 2009;38.

Barney B. M., P. C. Dos Santos, D. R. Dean, and L. C. Seefeldt. A substrate channel in the nitrogenase MoFe protein. J Biol Inorg Chem.. 2009;7:1015–1022.

Hoffman BM, D. R. Dean, and L. C. Seefeldt. Climbing Nitrogenase: Towards the mechanism of N2 reduction. Accounts of Chemical Research. 2009;19:609–619.

Seefeldt LC, B. M. Hoffman, and D. R. Dean. Lance Seefeldt, Brian Hoffman, and Dennis R. Dean. Annual Reviews of Biochemistry. 2009;78:701–722.

Setubal J. C., P.C. dos Santos, B. S. Goldman, H. Ertesvåg, G. Espin ,L. M Rubio, S. Valla, N. F. Almeida, D. Balasubramanian ,L. Cromes ,L. Curatti ,Z. Du, E. Godsy, B. Goodner, K. Hellner-Burris, J. A. Hernandez, K. Houmiel ,J. Imperial, C. Kennedy ,T. J. Larson, P. Latreille ,L. S. Ligon ,J. Lu M. Maerk, N. M. Miller, S. Norton, I. P. O'Carroll, I. Paulsen, E. C Raulfs, R. Roemer, J. Rosser, D. Segura, S. Slater, S. L. Stricklin ,D. J. Studholme, J. Sun, C. J. Viana, E. Wallin ,B. Wang, C. Wheeler, H. Zhu, D. R. Dean, R. Dixon.   R and D Wood. Genome sequence of Azotobacter vinelandii, an obligate aerobe specialized to support diverse anaerobic metabolic processes. J Bacteriol.. 2009;191:4534–4545.

2012 - Fellow of the American Association for the Advancement of Science 

2010 - Fellow of the American Academy of Microbiology

2009 - University Distinguished Professor 

2005 - Stroobants Professor of Biotechnology