title: The RimL transacetylase provides resistance to translation inhibitor microcin C.
abstract: Peptide-nucleotide antibiotic microcin C (McC) is produced by some Escherichia coli strains. Inside a sensitive cell, McC is processed, releasing a nonhydrolyzable analog of aspartyl-adenylate, which inhibits aspartyl-tRNA synthetase. The product of mccE, a gene from the plasmid-borne McC biosynthetic cluster, acetylates processed McC, converting it into a nontoxic compound. MccE is homologous to chromosomally encoded acetyltransferases RimI, RimJ, and RimL, which acetylate, correspondingly, the N termini of ribosomal proteins S18, S5, and L12. Here, we show that E. coli RimL, but not other Rim acetyltransferases, provides a basal level of resistance to McC and various toxic nonhydrolyzable aminoacyl adenylates. RimL acts by acetylating processed McC, which along with ribosomal protein L12 should be considered a natural RimL substrate. When overproduced, RimL also makes cells resistant to albomycin, an antibiotic that upon intracellular processing gives rise to a seryl-thioribosyl pyrimidine that targets seryl-tRNA synthetase. We further show that E. coli YhhY, a protein related to Rim acetyltransferases but without a known function, is also able to detoxify several nonhydrolyzable aminoacyl adenylates but not processed McC. We propose that RimL and YhhY protect bacteria from various toxic aminoacyl nucleotides, either exogenous or those generated inside the cell during normal metabolism.
authors.affiliation: Waksman Institute, Piscataway, New Jersey, USA.
authors.forename: Teymur
authors.initials: T
authors.lastname: Kazakov
authors.affiliation: Waksman Institute, Piscataway, New Jersey, USA.
authors.forename: Konstantin
authors.initials: K
authors.lastname: Kuznedelov
authors.affiliation: Waksman Institute, Piscataway, New Jersey, USA.
authors.forename: Ekaterina
authors.initials: E
authors.lastname: Semenova
authors.affiliation: Waksman Institute, Piscataway, New Jersey, USA.
authors.forename: Damir
authors.initials: D
authors.lastname: Mukhamedyarov
authors.affiliation: Purdue University, West Lafayette, Indiana, USA.
authors.forename: Kirill A
authors.initials: KA
authors.lastname: Datsenko
authors.affiliation: Institute of Molecular Genetics, Russian Academy of Sciences, Moscow, Russia.
authors.forename: Anastasija
authors.initials: A
authors.lastname: Metlitskaya
authors.affiliation: Laboratory of Medicinal Chemistry, Rega Institute for Medical Research, K.U. Leuven, Leuven, Belgium.
authors.forename: Gaston H
authors.initials: GH
authors.lastname: Vondenhoff
authors.affiliation: Institute of Gene Biology, Russian Academy of Sciences, Moscow, Russia.
authors.forename: Anton
authors.initials: A
authors.lastname: Tikhonov
authors.affiliation: University of Illinois, Urbana, Illinois, USA.
authors.forename: Vinayak
authors.initials: V
authors.lastname: Agarwal
authors.affiliation: University of Illinois, Urbana, Illinois, USA.
authors.forename: Satish
authors.initials: S
authors.lastname: Nair
authors.affiliation: Laboratory of Medicinal Chemistry, Rega Institute for Medical Research, K.U. Leuven, Leuven, Belgium.
authors.forename: Arthur
authors.initials: A
authors.lastname: Van Aerschot
authors.affiliation: Waksman Institute, Piscataway, New Jersey, USA Institute of Molecular Genetics, Russian Academy of Sciences, Moscow, Russia St. Petersburg State Polytechnical University, St. Petersburg, Russia Institute of Gene Biology, Russian Academy of Sciences, Moscow, Russia Skolkovo Institute of Science and Technology, Skolkovo, Russia severik@waksman.rutgers.edu.
authors.forename: Konstantin
authors.initials: K
authors.lastname: Severinov
mesh_terms: D000123:Acetyltransferases / Q000235:genetics / Q000378:metabolism*; D000249:Adenosine Monophosphate / Q000031:analogs & derivatives* / Q000737:chemistry / Q000378:metabolism / Q000633:toxicity*; D001224:Aspartic Acid / Q000031:analogs & derivatives* / Q000737:chemistry / Q000378:metabolism / Q000633:toxicity; D001430:Bacteriocins / Q000737:chemistry / Q000378:metabolism*; D004926:Escherichia coli / Q000187:drug effects / Q000201:enzymology* / Q000235:genetics / Q000378:metabolism; D029968:Escherichia coli Proteins / Q000235:genetics / Q000378:metabolism*; D010442:Peptide Chain Initiation, Translational / Q000187:drug effects
chemical_list: D001430:Bacteriocins; D029968:Escherichia coli Proteins; C020411:microcin; C052755:aspartyl adenylate; D001224:Aspartic Acid; D000249:Adenosine Monophosphate; D000123:Acetyltransferases; C521051:RimL protein, E coli