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, Beom Seok Kim, Cheol Oh Hyun, David H. Sherman, Yeo Joon Yoon

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

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
Volume347
Issue number10
DOIs
Publication statusPublished - 2005 Aug 1

Fingerprint

Mixed Function Oxygenases
Cytochrome P-450 Enzyme System
Macrolides
Oleandomycin
Substrates
Hydroxylation
Biosynthesis
Erythromycin
Plasticity
Oxidoreductases
Enzymes
Oxidation
Biosynthetic Pathways

Keywords

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

ASJC Scopus subject areas

  • Catalysis
  • Chemistry (miscellaneous)
  • Organic Chemistry

Cite this

Sang, K. L., Basnet, D. B., Hong, J. S. J., Won, S. J., Cha, Y. C., Hei, C. L., ... Yoon, Y. J. (2005). Structural diversification of macrolactones by substrate-flexible cytochrome P450 monooxygenases. Advanced Synthesis and Catalysis, 347(10), 1369-1378. https://doi.org/10.1002/adsc.200404354

Structural diversification of macrolactones by substrate-flexible cytochrome P450 monooxygenases. / Sang, Kil Lee; Basnet, Devi B.; Hong, Jay Sung Joong; Won, Seok Jung; Cha, Yong Choi; Hei, Chan Lee; Jae, Kyung Sohng; Keun, Garp Ryu; Dae, Joong Kim; Jong, Seog Ahn; Kim, Beom Seok; Hyun, Cheol Oh; Sherman, David H.; Yoon, Yeo Joon.

In: Advanced Synthesis and Catalysis, Vol. 347, No. 10, 01.08.2005, p. 1369-1378.

Research output: Contribution to journalArticle

Sang, KL, Basnet, DB, Hong, JSJ, Won, SJ, Cha, YC, Hei, CL, Jae, KS, Keun, GR, Dae, JK, Jong, SA, Kim, BS, Hyun, CO, Sherman, DH & Yoon, YJ 2005, 'Structural diversification of macrolactones by substrate-flexible cytochrome P450 monooxygenases', Advanced Synthesis and Catalysis, vol. 347, no. 10, pp. 1369-1378. https://doi.org/10.1002/adsc.200404354
Sang, Kil Lee ; Basnet, Devi B. ; Hong, Jay Sung Joong ; Won, Seok Jung ; Cha, Yong Choi ; Hei, Chan Lee ; Jae, Kyung Sohng ; Keun, Garp Ryu ; Dae, Joong Kim ; Jong, Seog Ahn ; Kim, Beom Seok ; Hyun, Cheol Oh ; Sherman, David H. ; Yoon, Yeo Joon. / Structural diversification of macrolactones by substrate-flexible cytochrome P450 monooxygenases. In: Advanced Synthesis and Catalysis. 2005 ; Vol. 347, No. 10. pp. 1369-1378.
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