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You are here: FRIAS Fellows Fellows 2020/21 Prof. Dr. Patricia C. Dos Santos

Prof. Dr. Patricia C. Dos Santos

Wake Forest University
External Senior Fellow
September 2018 - July 2019


Patricia Dos Santos is an associate professor and director of graduate studies in the Department of Chemistry at Wake Forest University. She was born in Porto Alegre, Brazil, where she received a B.S. in Pharmacy from the Federal University of the Rio Grande do Sul. In 2001 she moved to U.S.A. for her graduate studies at Virginia Tech, Blacksburg, VA. She obtained a PhD in 2004 with Dennis Dean. Her dissertation work involved the use of a combination microbial genetics, biochemical, and spectroscopic teachniques to studied the „Biosynthesis and Function of Nitrogenase Metalloclusters“. She remained at Virginia Tech for her post-doctoral work and received a NSF-Advance fellowship to initiate her indenpendent research program. She joined the Chemistry faculty at Wake Forest University in 2008 and was promoted to associate tenured professor in 2014. Dos Santos also holds a faculty appointment in the Department of Microbiology and Immunology at Wake Forest School of Medicine and serves as outreach director of the WFU Translational Science Center. 

Her research interests concentrates in the functional and mechanistic assignment of biochemical pathways in bacteria including the biosynthesis of Fe-S cluster, thionucleosides, and small molecules thiols as well as the study of biological nitrogen fixation in free living bacteria. In 2018, she has been awarded the Robert & Debra Lee Faculty Fellowship and the Reynolds Research Leave  that will provide support for a research sabbatical in the laboratory of Professor Einsle at the University of Freiburg during the academic year of 2018-2019.

Selected Publications

  • Dos Santos PC. Bacillus subtilis as a model for studying the assembly of Fe-S clusters in Gram-positive bacteria. Methods in Enzymol. 595, 185-212 (2017)
  • Dos Santos P.C. and Dean D.R. NIF system for simple [Fe-S] cluster assembly in nitrogen fixing bacteria. Encyclopedia of Inorganic and Bioinorganic Chemistry, Metalloprotein Active Site Assembly, Robert Scott and Michael K. Johnson (editors), Wiley 1-13 (2017).
  • Black KA, Dos Santos PC. Shared-intermediates in the biosynthesis of thio-cofactors: mechanism and functions of cysteine desulfurases and sulfur acceptors. BBA – Molecular Cell Research. 1853(6): 1470-1480 (2015)
  • Selbach BP, Chung AH, Scott AD, George SJ, Cramer SP, Dos Santos PC. Fe-S Cluster Biogenesis in Gram-Positive Bacteria: SufU Is a Zinc-Dependent Sulfur Transfer Protein. Biochemistry, 53(1):152-160 (2014).
  • Dos Santos PC, Fang Z, Mason S W, Setubal JC and Dixon R. Distribution of nitrogen fixation and nitrogenase-like sequences amongst microbial genomes. BMC Genomics, 13:162 (2012).

FRIAS Research Project

Mechanistic and structural investigation of nitrogen fixation proteins

Atmospheric nitrogen gas (N2) is the most abundant nitrogen source in the environment. In the global nitrogen cycle, N2 can be converted into a biologically usable form, ammonia (NH3), through a process known as nitrogen fixation.  Biological nitrogen fixation is crucial for life on Earth since it contributes approximately 60% of the total pool of fixed nitrogen and supplies usable nitrogen for other forms of life .  All N2 fixing organisms identified to date produce molybdenum-containing nitrogenase.  A select number of diazotrophs also contain additional paralogous enzymes, namely the vanadium-containing nitrogenase and an iron-only nitrogenase. While nitrogenase is the catalyst of nitrogen fixation in these biological systems, a consortium of additional gene products is required for the synthesis, activation and catalytic competency of this oxygen-sensitive metalloenzyme. Thus the biochemical complexity of this process often requires functional studies and isolation of gene products from the native nitrogen fixing organisms.

In this project, we will exploit the the strict aerobe diazotrophic bacterium Azotobacter vinelandii to gain insight into the structure and function of proteins enabling nitrogen fixation in this organism. In collaboration with Professor Oliver Einsle and his group from the Institute of Bichemistry at University of Freiburg, we will employ targeted genomic manipulation to construct A. vinelandii strains suibtable for direct isolation of proteins involved in nitrogen fixation under different physiological conditions and genetic backgrounds. Subsequent characterization of these proteins with associated metal cofactors will be completed using a combination of spectrocopic methods including X-ray protein crystallography.  This project aims to uncover molecular details associated with the synthesis of metallocofactors involved nitrogen fixation and to exploit this model system to understand the synthesis of other sulfur-containing cofactors in bacteria.