Structural diversification of macrolactones by substrate-flexible cytochrome P450 monooxygenases

Kil Lee Sang, Devi B. Basnet, Jay Sung Joong Hong, Seok Jung Won, Yong Choi Cha, Chan Lee Hei, Kyung Sohng Jae, Garp Ryu Keun, Joong Kim Dae, Seog Ahn Jong, Seok Kim Beom, Cheol Oh Hyun, David H. Sherman, Yeo Joon Yoon

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19 Citations (Scopus)


The substrate flexibilities of several cytochrome P450 monooxygenases involved in macrolide biosynthesis were investigated to test their potential for the generation of novel macrolides. PikC hydroxylase in the pikromycin producer Streptomyces venezuelae accepted oleandomycin as an alternative substrate and introduced a hydroxy group at the C-4 position, which is different from the intrinsic C-12 hydroxylation position in the natural substrate. This is the first report of C-4 hydroxylation activity of cytochrome P450 monooxygenase involved in the biosynthesis of 14-membered macrolides. EryF hydroxylase from the erythromycin biosynthetic pathway of Saccharopolyspora erythraea and OleP oxidase from the oleandomycin biosynthetic pathway of Streptomyces antibioticus also showed a certain degree of plasticity towards alternative substrates. In particular, EryF and OleP were found to oxidize a 12-membered macrolactone as an alternative substrate. These results demonstrate the potential usefulness of these enzymes to diversify macrolactones by post-PKS oxidations.

Original languageEnglish
Pages (from-to)1369-1378
Number of pages10
JournalAdvanced Synthesis and Catalysis
Issue number10
Publication statusPublished - 2005 Aug


  • Cytochrome P450 monooxygenase
  • Hydroxylation
  • Macrolide
  • Streptomyces
  • Substrate flexibility

ASJC Scopus subject areas

  • Catalysis
  • Organic Chemistry


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