Purification and characterization of sequential cobalamin-dependent radical SAM methylases ThnK and TokK in carbapenem β-lactam antibiotic biosynthesis.

Erica K Sinner, Craig A Townsend
Author Information
  1. Erica K Sinner: Department of Chemistry, Johns Hopkins University, Baltimore, MD, United States.
  2. Craig A Townsend: Department of Chemistry, Johns Hopkins University, Baltimore, MD, United States. Electronic address: ctownsend@jhu.edu.

Abstract

ThnK and TokK are cobalamin-dependent radical S-adenosylmethionine enzymes that catalyze sequential methylations of a common carbapenem biosynthetic intermediate. ThnK was an early characterized member of the subfamily of cobalamin-dependent radical S-adenosylmethionine enzymes. Since initial publication of the ThnK function, the field has progressed, and we have made methodological strides in the expression and purification of this enzyme and its ortholog TokK. An optimized protocol for obtaining the enzymes in pure and active form has enabled us to characterize their reactions and gain greater insight into the kinetic behavior of the sequential methylations they catalyze. We share here the methods and strategy that we have developed through our study of these enzymes.

Keywords

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Grants

  1. R01 AI121072/NIAID NIH HHS

MeSH Term

Anti-Bacterial Agents
Carbapenems
Methyltransferases
S-Adenosylmethionine
Vitamin B 12

Chemicals

Anti-Bacterial Agents
Carbapenems
S-Adenosylmethionine
Methyltransferases
Vitamin B 12

Word Cloud

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