Biochemistry and Molecular Biology
Penn State Science
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Carsten Krebs

Carsten Krebs

Main Content

  • Professor of Chemistry and
  • Professor of Biochemistry and Molecular Biology
332 Chemistry Building
University Park, PA 16802
Phone: (814) 865-6089

Research Interests

Bioinorganic chemistry- spectroscopic and kinetic studies on the mechanisms of iron-containing enzymes

Graduate Programs


Research Summary

Bioinorganic Chemistry - spectroscopic and kinetic studies on the mechanisms of iron-containing enzymes

Enzymes that contain the transition metal iron in their active sites exhibit great structural and functional diversity and play important roles in almost every aspect of life. The goal of our interdisciplinary research program is to combine biochemical, kinetic, and spectroscopic methods to study Fe-containing enzymes. The main technique used in our laboratory is 57Fe-Mössbauer spectroscopy. This technique provides information about oxidation state, spin state, coordination environment, and nuclearity of all chemically distinct iron species contained in a sample. In addition, it is possible to quantify all iron species. We combine this method with the rapid freeze quench (RFQ) method, and this allows us to monitor changes occuring at an iron site during a biochemical reaction. These studies (in conjunction with other techniques, such as stopped-flow absorption or RFQ EPR) provide detailed insight into the reaction mechanisms of iron-containing proteins.

Non-heme enzymes

Our main focus in this area is the oxygen activation reaction of the Fe(II) and α-ketoglutarate(α -KG)-dependent dioxygenase enzyme family. These enzymes play important roles in biochemistry (oxygen sensing and initiation of response to hypoxia, DNA repair, biosynthesis of antibiotics, etc) and they are believed to operate by a common mechanism. In collaboration with the group of J. Martin Bollinger, Jr., we study one member of this class, taurine: α -KG dioxygenase (TauD), and we identified the first reaction intermediate observed in this class of enzymes. This species contains a Fe=O unit, in which the iron is formally in the oxidation state +IV in the high-spin (S= 2) configuration. This species is the key species that abstracts an H-atom from the substrate for subsequent hydroxylation.

Iron-sulfur cluster enzymes

Our main focus in this area is the study of the ‘Radical-SAM’ enzymes. These enzymes utilize a reduced [4Fe-4S] cluster to cleave S-adenosylmethionine (SAM) to methionine and a 5’-deoxyadenosylradical (5’-dAdo•) intermediate. The 5’-dAdo• is then used for various purposes. For example, we study the enzyme lipoate synthase using 57Fe-Mössbauer spectroscopy with the group of Squire J. Booker.  

Selected Publications

  • 2015

    Rajakovich, L. J.; Nørgaard, H.; Warui, D. M.; Chang, W.-c.; Booker, S. J.; Krebs, C.; Bollinger, J. M., Jr.; Pandelia, M.-E.; “Rapid Reduction of the Diferric-Peroxyhemiacetal Intermediate in Aldehyde-Deformylating Oxygenase by a Cyanobacterial Ferredoxin: Evidence for a Free-Radical Mechanism” J. Am. Chem. Soc.  accepted DOI: 10.1021/jacs.5b06345 [link to publisher’s website]

    Livada, J.; Martinie, R. J.; Dassama, L. M. K.; Krebs, C.; Bollinger, J. M., Jr.; Silakov, A. “Direct Measurement of the Radical Translocation Distance in the Class I Ribonucleotide Reductase from Chlamydia trachomatis” J. Phys. Chem. B 2015, ASAP DOI: 10.1021/acs.jpcb.5b04067 [link to publisher’s website]

    Martinie, R. J.; Livada, J.; Chang, W.-c.; Green, M. T.; Krebs, C.; Bollinger, J. M., Jr.; Silakov, A. “Experimental Correlation of Substrate Position with Reaction Outcome in the Aliphatic Halogenase, SyrB2” J. Am. Chem. Soc. 2015, 137, 6912-6919. [link to publisher’s website]

    Bollinger, J. M., Jr.; Chang, W.-c.; Matthews, M. L.; Martinie, R. J.; Boal, A. K.; Krebs, C. “Mechanisms of 2-Oxoglutarate-Dependent Oxygenases: The Hydroxylation Paradigm and Beyond” in “2-Oxoglutarate-Dependent Oxygenases” Hausinger, R. P. and Schofield, C. J.; The Royal Society of Chemistry, London, 2015, 95-122. [link to publisher’s website]


    Chang, W.-c.; Guo, Y.; Wang, C.; Butch. S. E.; Rosenzweig, A. C.; Boal, A. K.; Krebs, C.; Bollinger, J. M., Jr. “Mechanism of the C5 Stereoinversion Reaction in the Biosynthesis of Carbapenem Antibiotics” Science 2014, 343, 1140-1144. [link to publisher’s website]

    Matthews, M. L.; Chang, W.-c.; Layne, A. P.; Miles, L. A.; Krebs, C.; Bollinger, J. M., Jr. “Direct Nitration and Azidation of Aliphatic Carbons by an Iron-Dependent Halogenase” Nature Chem. Biol. 2014, 10, 209-215. [link to publisher’s website]


    Wang, C.; Chang, W.-c.; Guo, Y.; Huang, H.; Peck, S. C.; Pandelia, M.-E.; Lin, G. M.; Liu, H. W.; Krebs, C.; Bollinger, J. M., Jr. “Evidence that the Fosfomycin-Producing Epoxidase, HppE, Is a Non–Heme-Iron Peroxidase” Science 2013, 342, 991-995. [link to publisher’s website]

    Wong, S. D.; Srnec, M.; Matthews, M. L.; Liu, L. V.; Kwak, Y.; Park, K.; Bell, C. B.; Alp, E. E.;  Zhao, J.; Yoda, Y.; Kitao, S.; Seto, M.; Krebs, C.; Bollinger, J. M., Jr.; Solomon, E. I. “Elucidation of the Fe(IV)=O Intermediate in the Catalytic Cycle of the Halogenase SyrB2” Nature 2013, 499, 320-324. [link to publisher’s website]

    Pandelia, M.-E.; Li, N.; Nørgaard, H.; Warui, D. M.; Rajakovich, L. J.; Chang, W.-c.; Booker, S. J.; Krebs, C.; Bollinger, J. M., Jr. “Substrate-Triggered Addition of Dioxygen to the Diferrous Cofactor of Aldehyde-Deformylating Oxygenase to Form a Diferric-Peroxide Intermediate” J. Am. Chem. Soc.2013, 135, 15801−15812. [link to publisher’s website]

    Wörsdörfer, B.; Conner, D. A.; Yokoyama, K.; Livada, J.; Seyedsayamdost, M.; Jiang, W.; Stubbe, J.; Bollinger, J. M., Jr.; Krebs, C. “Function of the Diiron Cluster of Escherichia coli Class Ia Ribonucleotide Reductase in Proton-Coupled Electron Transfer” J. Am. Chem. Soc. 2013, 135, 8585−8593. [link to publisher’s website]

    Krebs, C.; Dassama, L. M. K.; Matthews, M. L.; Jiang, W.; Price, J. C.; Korboukh, V.; Li, N.; Bollinger, J. M., Jr. “Novel Approaches for the Accumulation of Oxygenated Intermediates to Multi-Millimolar Concentrations” Coord. Chem. Rev. 2013, 257, 234-243. [link to publisher’s website]


    Dassama, L. M. K.; Yosca, T. H.; Conner, D. A.; Lee, M.; Blanc, B.; Streit, B. R.; Green, M. T.; DuBois, J. L.; Krebs, C., Bollinger, J. M., Jr. “O2-Evolving Chlorite Dismutase as a Tool to Study O2-Utilizing Enzymes” Biochemistry, 2012, 51, 1607-1616. [link to publisher’s website]


    Krebs, C., Bollinger, J. M., Jr.; Booker, S. J. “Cyanobacterial Alkane Biosynthesis Further Expands the Catalytic Repertoire of the Ferritin-Like “Di-Iron-Carboxylate” Proteins” Curr. Opin. Chem. Biol. 2011, 15, 291-303. [link to publisher’s website]

    Warui, D. M.; Li, N.; Nørgaard, H.; Krebs, C., Bollinger, J. M., Jr.; Booker, S. J. “Detection of Formate, Rather than Carbon Monoxide, as the Stoichiometric Co-Product in Conversion of Fatty Aldehydes to Alkanes by a Cyanobacterial Aldehyde Decarbonylase” J. Am. Chem. Soc. 2011, 133, 3316-3319. [link to publisher’s website]


    van der Donk, W. A.; Krebs, C.; Bollinger, J. M., Jr. “Substrate Activation by Iron Superoxo Intermediates” Curr. Opin. Struct. Biol., 2010, 20, 673–683. [link to publisher’s website]

    Li, N.; Korneeva Korboukh, V.; Krebs, C.; Bollinger, J. M., Jr. “Four-Electron Oxidation of p-Hydroxylaminobenzoate to p-Nitrobenzoate by a Peroxodiferric Complex in AurF from Streptomyces thioluteus” Proc. Natl. Acad. Sci., U. S. A., 2010, 107, 15722–15727. [link to publisher’s website]


    Matthews, M. L.; Neumann, C. S.; Miles, L. A.; Grove, T. L.; Booker, S. J.; Krebs, C.; Walsh, C. T.; Bollinger, J. M., Jr. “Substrate Positioning Controls the Partition between Halogenation and Hydroxylation in the Aliphatic Halogenase, SyrB2” Proc. Natl. Acad. Sci., U. S. A., 2009, 106, 17723-17728. [link to publisher’s website]


    Bollinger, J. M., Jr.; Jiang, W.; Green, M. T.; Krebs, C. “The Manganese(IV)/Iron(III) Cofactor of Chlamydia trachomatis Ribonucleotide Reductase: Structure, Assembly, Radical Initiation, and Evolution” Curr. Opin. Struct. Biol., 2008, 18, 650-657. [link to publisher’s website]


    Krebs, C.; Galonić Fujimori, D.; Barr, E. W.; Walsh, C. T.; Bollinger, J. M., Jr. “Non-heme Fe(IV)-Oxo Intermediates” Acc. Chem. Res., 2007, 40, 484-492. [link to publisher’s website]

    Jiang, W.; Yun, D.; Saleh, L.; Barr, E. W.; Xing, G.; Hoffart, L. M.; Maslak, M.-A.; Krebs, C.; Bollinger, J. M., Jr. “A Stable Manganese(IV)/Iron(III) Cofactor Initiates Substrate Radical Production in Chlamydia trachomatis Ribonucleotide Reductase” Science, 2007, 316, 1188-1191. [link to publisher’s website]

    Bollinger, J. M., Jr.; Krebs, C. “Enzymatic C-H Activation by Metal-Superoxo Intermediates” Curr. Opin. Chem. Biol., 2007, 11, 151-158. [link to publisher’s website]

    Galonić, D. P.; Barr, E. W.; Walsh, C. T.; Bollinger, J. M., Jr.; Krebs, C. “Two Interconverting High-Spin Fe(IV) Intermediates in Aliphatic Chlorination by the Fe(II)- and α-Ketoglutarate-Dependent Halogenase CytC3” Nature Chem. Biol., 2007, 3, 113-116. [link to publisher’s website]


    Hoffart, L. M.; Barr, E. W.; Guyer, R. B.; Bollinger, J. M., Jr.; Krebs, C. “Direct Spectroscopic Detection of a C-H-Cleaving High-Spin Fe(IV) Complex in a Prolyl-4-Hydroxylase” Proc. Natl. Acad. Sci., U. S. A., 2006, 103, 14738-14743. [link to publisher’s website]

    Xing, G.; Diao, Y.; Hoffart, L. M.; Barr, E. W.; Prabhu, K. S.; Arner, R. J.; Reddy, C. C.; Krebs, C.; Bollinger, J. M., Jr. “Evidence for C-H Cleavage by an Iron-Superoxide Complex in the Glycol Cleavage Reaction Catalyzed by myo-Inositol Oxygenase” Proc. Natl. Acad. Sci. U.S.A. 2006, 103, 6130-6135. [link to publisher’s website]


    Krebs, C.; Price, J. C.; Baldwin, J.; Saleh, L.; Green, M. T.; Bollinger, J. M., Jr. “Rapid Freeze-Quench 57Fe Mössbauer Spectroscopy: Monitoring Changes of an Iron-Containing Active Site during a Biochemical Reaction” Inorg. Chem. 2005, 44, 742-757. [link to publisher’s website]


    Price, J. C.; Barr, E. W.; Tirupati, B.; Bollinger, J. M., Jr.; Krebs, C. “The First Direct Characterization of a High-Valent Iron Intermediate in the Reaction of an a-Ketoglutarate-Dependent Dioxygenase: A High-Spin Fe(IV) Complex in Taurine/a-Ketoglutarate Dioxygenase (TauD) from Escherichia coli” Biochemistry 2003, 42, 7497-7508. [link to publisher’s website]