Carnegie Mellon University

Yisong Guo

Yisong (Alex) Guo

Assistant Professor, Chemistry

  • Mellon Institute 552
  • 412-268-1704

Education

2003–2009     Ph.D. Department of Applied Science, University of California, Davis

Research

Spectroscopy, bioinorganic chemistry, Mössbauer and EPR spectroscopy, synchrotron radiation techniques, nuclear resonance vibrational spectroscopy (NRVS), synchrotron Mössbauer, metalloproteins, enzyme mechanisms, transition metal complexes, electronic structures, density functional theory.

Metalloproteins play essential roles in many key biological processes, including photosynthesis, respiration, nitrogen fixation and carbon cycle, antibiotics biosynthesis, gene regulation, post transcriptional modification, bio-signal sensing, and DNA/RNA repair. In these biological processes, an astounding array of chemical transformations with high stereo- and regio-selectivities is achieved by metal centers buried inside the protein scaffold of metalloproteins. Studies of these metal centers in both geometric and electronic level not only can help us reveal the fundamental chemical principles underpinning these biological processes, also provide valuable guidelines for designing and synthesizing efficient and inexpensive catalysts to perform some of these important yet challenging chemical transformations, such as water oxidation, dinitrogen reduction, selective C-H functionalization.

Our main research focus is iron containing metalloproteins, in particular, small molecule (N2, H2, O2 etc.) activating enzymes, such as nitrogenases, hydrogenases, and oxygenases. Various advanced spectroscopic methods are utilized to gain information regarding iron center changes, both geometric and electronic, during enzyme catalytic cycles. Spectroscopic studies are coupled with Density Functional Theory (DFT) calculations to establish structural models and further identify reaction mechanisms. The ultimate goal of our research is to impact favorably on alternative energy research and human health.

The spectroscopic methods we use include Mössbauer Spectroscopy, Electron Paramagnetic Resonance (EPR) Spectroscopy, Nuclear Resonance Vibrational Spectroscopy (NRVS), and Synchrotron Mössbauer.

Mössbauer spectroscopy arguably has the highest information content of any spectroscopic methods on studies of iron containing systems. It detects all iron in a given sample, and determines their oxidation, spin states, and precise quantification of iron in different local environments. It is a high-resolution technique, which allows one to probe the electronic structure of iron sites in great detail through the hyperfine coupling between electronic states and nuclear states. EPR spectroscopy is a high sensitivity technique; it detects paramagnetic systems and reveals their electronic structures through electronic Zeeman Effect.

Recent developments of synchrotron radiation (SR) facilities enable us to utilize SR sources for Mössbauer spectroscopy in replacement of traditional radioactive sources. The advantage of Synchrotron Mössbauer over the conventional lab-based Mössbauer is that it can have higher spectral resolution, shorter measurement time, and the capability of measuring smaller samples, which are crucial for studies on metalloproteins. The advancement of modern synchrotron radiation sources also promotes the development of a new type of vibrational spectroscopic technique, Nuclear Resonance Vibrational Spectroscopy (NRVS). NRVS detects nuclear excitation coupled molecular vibration excitation (or de-excitation), which conceptually resembles Raman scattering. Yet, compared with Raman and Infrared techniques, NRVS has much higher element selectivity and less restrictive selection rules. It allows us study structures and dynamics of iron centers in metalloproteins by selectively probing iron related vibrations in the far IR region (essentially down to 0 cm-1) without the interference of protein scaffold and solvent vibrations.

With continuous development of synchrotron radiation facilities, new synchrotron radiation with many orders of magnitude higher in intensity and extremely smaller beam size (sub-micron to nanometers) than those in use today will be available in the near future. In collaboration with groups at synchrotron radiation facilities, we will develop imaging techniques using Mössbauer spectroscopy to study iron cofactors in organelles and whole cells.

Publications

Insights into the Desaturation of Cyclopeptin and its C3 Epimer Catalyzed by a non-Heme Iron Enzyme: Structural Characterization and Mechanism Elucidation
Liao, H.-J., Li, J., Huang, J.-L., Davidson, M., Kurnikov, I., Lin, T.-S., Lee, J. L., Kurnikova, M., Guo, Y., Chan, N.-L. and Chang, W.-c., Angew. Chem. 2018. doi:10.1002/ange.201710567

CmlI N-Oxygenase Catalyzes the Final Three Steps in Chloramphenicol Biosynthesis without Dissociation of Intermediates
Anna J. Komor, Brent S. Rivard, Ruixi Fan, Yisong Guo, Lawrence Que, Jr., and John D. Lipscomb
Biochemistry, 56 (37), 4940-4950, 2017. DOI: 10.1021/acs.biochem.7b00695

O–H Activation by an Unexpected Ferryl Intermediate during Catalysis by 2-Hydroxyethylphosphonate Dioxygenase
Spencer C. Peck, Chen Wang, Laura M. K. Dassama, Bo Zhang, Yisong Guo, Lauren J. Rajakovich, J. Martin Bollinger, Jr., Carsten Krebs, and Wilfred A. van der Donk, J. Am. Chem. Soc., 139 (5), 2045-2052, 2017. DOI: 10.1021/jacs.6b12147

Time-dependent bacterial transcriptional response to CuO nanoparticles differs from that of Cu2+ and provides insights into CuO nanoparticle toxicity mechanisms
Joe D. Moore, Astrid Avellan, Clinton W. Noack, Yisong Guo, Gregory V. Lowry and Kelvin B. Gregory, Environ. Sci.: Nano, 2017, 4, 2321-2335, DOI: 10.1039/C7EN00600D (Paper)

Identification of a Catalytic Iron-Hydride at the H-cluster of [FeFe]-Hydrogenase
David W. Mulder, Yisong Guo, Michael W. Ratzloff, Paul W. King, J. Am. Chem. Soc. 2017, 139: 83-86.

The Two Faces of Tetramethylcyclam in Iron Chemistry: Distinct Fe-O-M Complexes Derived from [FeIV(Oanti/syn)(TMC)]2+ Isomers
Ang Zhou, Jai Prakash, Gregory Rohde, Johannes Klein, Scott Kleespies, Apparao Draksharapu, Ruixi Fan, Yisong Guo, Christopher Cramer, Lawrence Que Jr., Inorg. Chem. 56: 518-527, 2017.

Reactivity of an FeIV-Oxo Complex with Protons and Oxidants
Ethan A. Hill, Andrew C. Weitz, Elizabeth Onderko, Yisong Guo, Marcel Swart, Emile L. Bominaar, Michael T. Green, Michael P. Hendrich, David C. Lacy, Andy S. Borovik, J. Am. Chem. Soc. 138: 13143-13146, 2016.

The Nitrogenase FeMo-cofactor Precursor Formed by NifB Protein: A Diamagnetic Eight Iron Atoms
Yisong Guo, Carlos Echavarri-Erasun, Marie Demuez, Emilio Jiménez-Vicente, Emile L. Bominaar, Luis M. Rubio, Angew. Chem. Int. Ed. 41: 12764- 12767, 2016.

Mechanistic Investigation of a Non-Heme Iron Enzyme Catalyzed Epoxidation in (-)-4’-Methoxycyclopenin Biosynthesis
Wei-chen Chang, Jikun Li, Justin L. Lee, Andrea A. Cronican, Yisong Guo, J. Am. Chem. Soc. 2016, 138: 10390-10393.

Endoperoxide Formation by an α-Ketoglytarate-Dependent Mononuclear Non-Heme iron Enzyme
Wupeng Yan, Heng Song, Fuhang Song, Yisong Guo, Cheng-Hsuan Wu, Ampon Sae Her, Yi Pu, Shu Wang, Nathchar Naowarojna, Andrew Weitz, Michael P. Hendrich, Catherine E. Costello, Lixin Zhang, Pinghua Liu, Yan Jessie Zhang, Nature, 2015, 527: 539 – 543.

Mechanism of the C5 Stereoinversion Reaction in the Biosynthesis of Carbapenem Antibiotics
Wei-chen Chang, Yisong Guo, Chen Wang, Susan E. Butch, Amy C. Rosenzweig, Amie K. Boal, Carsten Krebs, J. Martin Bollinger Jr., Science, 2014, 343, 1040-1044.

Evidence that the Fosfomycin-Producing Epoxidase, HppE, Is a Non-Heme-Iron Peroxidase
Chen Wang, Wei-chen Chang, Yisong Guo, Hui Huang, Spencer C. Peck, Maria E. Pandelia, Geng-min Lin, Hung-wen Liu, Carsten Krebs, J. Martin Bollinger Jr., Science, 2013, 342, 991-995.

Synchrotron Radiation Based Nuclear Resonant Scattering: Applications to Bioinorganic Chemistry
Yisong Guo, Yoshitaka Yoda, Xiaowei Zhang, Yuming Xiao, Stephen P. Cramer, Book Chapter in Mössbauer Spectroscopy: Applications in Chemistry, Biology, Nanotechnology, Industry, and Environment, Wiley, 2013.

Nuclear Resonance Vibrational Spectroscopy (NRVS) of Rubredoxin and MoFe Protein Crystals
Yisong Guo, Eric Brecht, Kristen Aznavour, Jay C. Nix, Yuming Xiao, Hongxin Wang, Simon J. George, Robert Bau, Stephen Keable, John W. Peters, Michael W. W. Adams, Francis E. Jenney Jr. Wolfgang Sturhahn, E. Ercan Alp, Jiyong Zhao, Yoshitaka Yoda, Stephen P. Cramer, Hyperfine Interactions 2013, 222, S77-S90.

Appointments

YearsPosition
2014–present Assistant Professor, Department of Chemistry, Carnegie Mellon University
2012–2013 Postdoctoral Research Associate, Department of Chemistry, the Pennsylvania State University.
Advisors: Prof. J. Martin Bollinger and Prof. Carsten Krebs
2009–2012 Postdoctoral Research Associate, Department of Chemistry, Carnegie Mellon University.
Advisors: Prof. Eckard Münck and Prof. Emile L. Bominaar (theory)

Awards and Distinctions

YearsAward
2017 NSF CAREER Award