Quintuply orthogonal pyrrolysyl-tRNA synthetase/tRNA^Pyl pairs.

ABSTRACT: Mutually orthogonal aminoacyl transfer RNA synthetase/transfer RNA pairs provide a foundation for encoding non-canonical amino acids into proteins, and encoded non-canonical polymer and macrocycle synthesis. Here we discover quintuply orthogonal pyrrolysyl-tRNA synthetase (PylRS)/pyrrolysyl-tRNA (tRNA^Pyl) pairs. We discover empirical sequence identity thresholds for mutual orthogonality and use these for agglomerative clustering of PylRS and tRNA^Pyl sequences; this defines numerous sequence clusters, spanning five classes of PylRS/tRNA^Pyl pairs (the existing classes +N, A and B, and newly defined classes C and S). Most of the PylRS clusters belong to classes that were unexplored for orthogonal pair generation. By testing pairs from distinct clusters and cla

SUBMITTER: Beattie AT 

PROVIDER: S-EPMC7615293 | biostudies-literature | 2023 Jul

REPOSITORIES: biostudies-literature