[ChBE-Grad] UH ChBE Seminar this Friday, Sept 20

[Solano, Nicolette]

[William A. Brookshire Department of Chemical and Biomolecular Engineering Seminar Series]<https://www.chee.uh.edu>
Developing Improved Biosynthesis Pathways for
Non-Canonical Amino Acids

Ross Thyer, Ph.D.
Assistant Professor
Rice University

Friday, Sept 20 | 10:30am Central
Engineering room L2D2

LECTURE ABSTRACT

Non-canonical amino acids have proven valuable tools for augmenting protein function and offer an expansive array of protein chemistries beyond those found in the standard genetic code. While hundreds of new chemistries have now been introduced into proteins, two non-canonical amino acids of particular interest to protein engineers are the 21st amino acid, selenocysteine (Sec, U), and 3,4-dihydroxyphenylalanine or L-DOPA. Importantly, while both offer novel bioorthogonal chemistry, they are also naturally occurring, providing researchers with multiple model systems to study and serve as inspiration for new catalysts and materials.

Selenocysteine is a rare amino acid with an unusual mosaic distribution across the proteome. The amino acid is analogous to cysteine (Cys) but replaces the thiol with a selenol moiety allowing it to share similar but intensified chemical properties, including a high affinity for metals, strong nucleophilicity, and reversible covalent bond formation. These properties are of broad interest to the protein engineering community and have great potential for the development of new biologics stabilized with diselenide bonds and industrial biocatalysts. In contrast to both canonical amino acids and selenocysteine, L-DOPA is natively introduced into proteins as a post-translational modification of tyrosine residues. The amino acid is formed by direct oxidation of the tyrosine phenol group to form a catechol moiety, a reaction performed by several different enzymes and with varying degrees of selectivity for the free or incorporated amino acid. In Nature, the reactive catechol moiety frequently forms covalent crosslinks with nearby nucleophiles, bonds which play an important role in tuning the properties of many proteinaceous biomaterials.

Efforts to better understand the biosynthesis pathways for these two amino acids are a high priority; direct conversion of serine into selenocysteine is unfavourable and proceeds very slowly in comparison to the initial charging of the tRNA with serine. This can result in erroneous incorporation of serine into proteins, especially at high rates of translation and turn-over of the selenocysteinyl-tRNA pool. Similarly, selectivity of the engineered translational machinery for L-DOPA incorporation is not perfect, often resulting in misincorporation of tyrosine. The current lack of highly efficient biosynthesis pathways for these amino acids is a key barrier to large scale production of Sec- and DOPA-containing proteins. Here we present several efforts to identify, characterize, and improve enzymes involved in the biosynthesis of selenocysteine and L-DOPA, and discuss the development of novel assays and genetic reporter systems to facilitate high-throughput engineering.



SPEAKER BIOSKETCH

Dr. Thyer completed a B.Sc. (Hons) in biochemistry at the University of Western Australia and further completed a Ph.D. at the University of Western Australia in the laboratory of Dr. Oliver Rackham working on orthogonal translation systems. Dr. Thyer completed his postdoctoral work in the laboratory of Dr. Andrew Ellington at the University of Texas at Austin where he developed several new tools and methods for genetic code expansion and co-founded GRO Biosciences. In 2020, Dr. Thyer joined the Department of Chemical and Biomolecular Engineering at Rice University in Houston, Texas, as an assistant professor. His group uses protein engineering approaches to develop new therapeutics containing non-canonical amino acids, high-throughput genetic tools for engineering biosynthesis pathways and industrial biocatalysts, and novel microbial systems for sustainable biomanufacturing.





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[William A. Brookshire Department of Chemical and Biomolecular Engineering]<https://www.chee.uh.edu>

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