Natural product diversification using a non-natural cofactor analogue of S-adenosyl-L-methionine

Changsheng Zhang, Rachel L. Weller, Jon S. Thorson, Scott R. Rajski

Research output: Contribution to journalArticlepeer-review

66 Scopus citations


Adenosine analogues bearing either 5′-aziridine or 5′-N-mustard electrophiles are methyltransferase-dependent DNA alkylating agents. We present here a novel synthetic cofactor bearing a pendant 5′-amino acid N-mustard. Unlike previously studied synthetic cofactors, this material is very efficiently used by the natural product biosynthetic enzyme rebeccamycin methyltransferase (RebM) to generate a number of new rebeccamycin analogues. These data promote the notion that natural product methyltransferases can be used with non-natural cofactors to enhance the molecular diversity of natural product analogues for drug discovery. To our knowledge, this is the first documentation of a biological methyltransferase, other than DNA methyltransferases, that can exploit such synthetic cofactors.

Original languageEnglish
Pages (from-to)2760-2761
Number of pages2
JournalJournal of the American Chemical Society
Issue number9
StatePublished - Mar 8 2006

ASJC Scopus subject areas

  • Catalysis
  • General Chemistry
  • Biochemistry
  • Colloid and Surface Chemistry


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