Identification and characterization of mutations conferring resistance to D-amino acids in Bacillus subtilis

Journal of Bacteriology
Sara A LeimanRichard Losick

Abstract

Bacteria produce d-amino acids for incorporation into the peptidoglycan and certain nonribosomally produced peptides. However, D-amino acids are toxic if mischarged on tRNAs or misincorporated into protein. Common strains of the Gram-positive bacterium Bacillus subtilis are particularly sensitive to the growth-inhibitory effects of D-tyrosine due to the absence of D-aminoacyl-tRNA deacylase, an enzyme that prevents misincorporation of D-tyrosine and other D-amino acids into nascent proteins. We isolated spontaneous mutants of B. subtilis that survive in the presence of a mixture of D-leucine, D-methionine, D-tryptophan, and D-tyrosine. Whole-genome sequencing revealed that these strains harbored mutations affecting tRNA(Tyr) charging. Three of the most potent mutations enhanced the expression of the gene (tyrS) for tyrosyl-tRNA synthetase. In particular, resistance was conferred by mutations that destabilized the terminator hairpin of the tyrS riboswitch, as well as by a mutation that transformed a tRNA(Phe) into a tyrS riboswitch ligand. The most potent mutation, a substitution near the tyrosine recognition site of tyrosyl-tRNA synthetase, improved enzyme stereoselectivity. We conclude that these mutations promote the proper c...Continue Reading

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Citations

Dec 18, 2015·Proteins·Thomas SimonsonPierre Plateau
Dec 24, 2016·Molecular Microbiology·Richard J Lewis
Oct 14, 2017·The ISME Journal·Laura AlvarezFelipe Cava
Jan 10, 2017·Frontiers in Microbiology·Miguel A Naranjo-OrtízToni Gabaldón
Jan 14, 2017·Frontiers in Microbiology·Eyal RosenIlana Kolodkin-Gal

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