Methylations in complex carbapenem biosynthesis are catalyzed by a single cobalamin-dependent radical S-adenosylmethionine enzyme.

Erica K Sinner, Michael S Lichstrahl, Rongfeng Li, Daniel R Marous, Craig A Townsend
Author Information
  1. Erica K Sinner: Department of Chemistry, Johns Hopkins University, 3400 N Charles St., Baltimore, MD 21218, USA. ctownsend@jhu.edu.

Abstract

Complex carbapenem β-lactam antibiotics contain diverse C6 alkyl substituents constructed by cobalamin-dependent radical SAM enzymes. TokK installs the C6 isopropyl chain found in asparenomycin. Time-course analyses of TokK and its ortholog ThnK, which forms the C6 ethyl chain of thienamycin, indicate that catalysis occurs through a sequence of discrete, non-processive methyl transfers.

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Grants

  1. R01 AI014937/NIAID NIH HHS
  2. R01 AI121072/NIAID NIH HHS
  3. R56 AI014937/NIAID NIH HHS
  4. T32 GM080189/NIGMS NIH HHS

MeSH Term

Anti-Bacterial Agents
Carbapenems
Catalysis
Methionine Adenosyltransferase
Methylation
Vitamin B 12

Chemicals

Anti-Bacterial Agents
Carbapenems
Methionine Adenosyltransferase
Vitamin B 12

Word Cloud

Created with Highcharts 10.0.0C6carbapenemcobalamin-dependentradicalTokKchainComplexβ-lactamantibioticscontaindiversealkylsubstituentsconstructedSAMenzymesinstallsisopropylfoundasparenomycinTime-courseanalysesorthologThnKformsethylthienamycinindicatecatalysisoccurssequencediscretenon-processivemethyltransfersMethylationscomplexbiosynthesiscatalyzedsingleS-adenosylmethionineenzyme

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