Biosynthesis of epothilone intermediates with alternate starter units

Engineering polyketide-nonribosomal interfaces

Sarah E. O'Connor, Christopher T. Walsh*, Fei Liu

*Corresponding author for this work

Research output: Contribution to journalArticle

30 Citations (Scopus)

Abstract

The early steps of epothilone biosynthesis were reprogrammed in vitro by incorporating enzyme subunits (e.g. EntB, EntE) from other biosynthetic pathways into the epothilone (Epo) assembly line (see scheme). Recognition sequences identified at the C termini of the epothilone biosynthetic proteins enabled heterologous enzyme transfer when fused to noncognate proteins, as a step toward the reengineering of biosythetic pathways to produce natural product analogues in vivo.

Original languageEnglish
Pages (from-to)3917-3921
Number of pages5
JournalAngewandte Chemie - International Edition
Volume42
Issue number33
DOIs
Publication statusPublished - 25 Aug 2003
Externally publishedYes

Keywords

  • Antitumor agents
  • Biosynthesis
  • Enzyme catalysis
  • Polyketides
  • Protein modifications

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