Professor of Biochemistry and Biophysics
Ph.D. | Yale University, 1990
Post-Doctoral Research Fellow 1990-1994 | University of California, San Francisco
Our lab works in two areas of Biochemistry. First, we study how sulfur is taken up into single-celled microorganisms that inhabit environments without oxygen (anaerobes). This work is important because of its potential to inform us about the different biochemical mechanisms that were present on the early Earth, before about 2 billion years ago. We use methanogens as the model organism for our study. Methanogens produce methane, an important greenhouse gas, as a byproduct of their metabolism.
We understand sulfur uptake and incorporation into biomolecules well in common bacteria and higher organisms that live in oxygen-rich environments. However, the known genes that specify proteins involved in these processes are missing in many methanogens. By computational analysis of genomic DNA sequences from all microorganisms in the domain Archaea, including methanogens, we discovered three new genes that were likely candidates to be involved in anaerobic sulfur biochemistry. We then used genetics to demonstrate that the proteins coded by these genes are essential to sulfur metabolism under certain conditions. We are now studying the new proteins intensively using techniques from molecular biology, biochemistry and biophysics, including X-ray crystallography.
The other project is in the area of synthetic biology, a new field devoted to the re-engineering of living cells toward new useful functions in environmental remediation, biosynthesis of therapeutics, and many other areas. We focus on engineering of the cellular apparatus for protein synthesis, especially with respect to the coding enzymes (the aminoacyl-tRNA synthetases) that properly match amino acids and tRNAs. For this project we draw on many years of experience in studying the fundamental catalytic mechanisms of these and related enzymes that are involved in the biochemistry of transfer RNA (tRNA).
Our current work in this field involves the mechanistic dissection and rational engineering of aminoacyl-tRNA synthetases that are able to incorporate noncanonical amino acids, such as 3-nitrotyrosine, in response to engineered genes containing stop codons. Many aminoacyl-tRNA synthetases that work with noncanonical amino acids are derived from directed evolution approaches, but they are not as catalytically efficient as the naturally occurring enzymes. There are also important questions regarding the ability of other parts of the protein synthesis apparatus, such as elongation factors and ribosomes, to function with the new aminoacylated tRNAs. We hope that our detailed understanding of structure-function relationships will be helpful in solving some of the practical challenges in this area of synthetic biology.
Our lab is also affiliated with the Center for Life in Extreme Environments at PSU and the Department of Biochemistry and Molecular Biology at Oregon Health Sciences University (OHSU).
- Perona JJ & Gruic-Sovulj I. Synthetic and editing mechanisms of aminoacyl-tRNA synthetases. Top. Current Chem. 344, 1-41 (2014).
- Bhaskaran H, Taniguchi T, Suzuki T, Suzuki T & Perona JJ. Structural dynamics of a mitochondrial tRNA possessing weak thermodynamic stability. Biochemistry 53, 1456-1465 (2014).
- Hadd A & Perona JJ. Coevolution of specificity determinants in eukaryotic glutamyl- and glutaminyl-tRNA synthetases. J. Mol. Biol. 426, 3619-3633 (2014).
- Dulic M, Perona JJ & Gruic-Sovulj I. Determinants for tRNA-dependent pre-transfer editing in the synthetic site of isoleucyl-tRNA synthetase. Biochemistry 53, 6189-6198 (2014).
- Hadd A & Perona JJ. Recoding aminoacyl-tRNA synthetases for synthetic biology by rational protein-RNA engineering. ACS Chem. Biol. 9, 2761-2766 (2014).
- Rauch BJ, Gustafson A & Perona JJ. Novel proteins for homocysteine biosynthesis in anaerobic microorganisms. Mol. Microbiol. 94, 1330-1342 (2014).
- Allen KD, Miller DV, Rauch BJ, Perona JJ & White RH. Homocysteine is biosynthesized from aspartate semialdehyde and hydrogen sulfide in methanogenic archaea. Biochemistry 54, 3129-3132 (2015).