Structure of OxyAtei : Completing our picture of the glycopeptide antibiotic producing Cytochrome P450 cascade

Kristina Haslinger, Max J. Cryle

Research output: Contribution to journalArticleResearchpeer-review

Abstract

Cyclization of glycopeptide antibiotic precursors occurs in either three or four steps catalyzed by Cytochrome P450 enzymes. Three of these enzymes have been structurally characterized to date with the second enzyme along the pathway, OxyA, escaping structural analysis. We are now able to present the structure of OxyAtei involved in teicoplanin biosynthesis - the same enzyme recently shown to be the first active OxyA homolog. In spite of the hydrophobic character of the teicoplanin precursor, the polar active site of OxyAtei and its affinity for certain azole inhibitors hint at its preference for substrates with polar decorations.
Original languageEnglish
Pages (from-to)571-581
Number of pages11
JournalFEBS Letters
Volume590
Issue number4
DOIs
Publication statusPublished - Feb 2016

Keywords

  • Cytochrome P450
  • glycopeptide antibiotics
  • nonribosomal peptide synthesis
  • phenolic coupling
  • teicoplanin

Cite this

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Structure of OxyAtei : Completing our picture of the glycopeptide antibiotic producing Cytochrome P450 cascade. / Haslinger, Kristina; Cryle, Max J.

In: FEBS Letters, Vol. 590, No. 4, 02.2016, p. 571-581.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - Structure of OxyAtei

T2 - Completing our picture of the glycopeptide antibiotic producing Cytochrome P450 cascade

AU - Haslinger, Kristina

AU - Cryle, Max J.

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Y1 - 2016/2

N2 - Cyclization of glycopeptide antibiotic precursors occurs in either three or four steps catalyzed by Cytochrome P450 enzymes. Three of these enzymes have been structurally characterized to date with the second enzyme along the pathway, OxyA, escaping structural analysis. We are now able to present the structure of OxyAtei involved in teicoplanin biosynthesis - the same enzyme recently shown to be the first active OxyA homolog. In spite of the hydrophobic character of the teicoplanin precursor, the polar active site of OxyAtei and its affinity for certain azole inhibitors hint at its preference for substrates with polar decorations.

AB - Cyclization of glycopeptide antibiotic precursors occurs in either three or four steps catalyzed by Cytochrome P450 enzymes. Three of these enzymes have been structurally characterized to date with the second enzyme along the pathway, OxyA, escaping structural analysis. We are now able to present the structure of OxyAtei involved in teicoplanin biosynthesis - the same enzyme recently shown to be the first active OxyA homolog. In spite of the hydrophobic character of the teicoplanin precursor, the polar active site of OxyAtei and its affinity for certain azole inhibitors hint at its preference for substrates with polar decorations.

KW - Cytochrome P450

KW - glycopeptide antibiotics

KW - nonribosomal peptide synthesis

KW - phenolic coupling

KW - teicoplanin

UR - http://www.ncbi.nlm.nih.gov/pubmed/26820384

U2 - 10.1002/1873-3468.12081

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