Structural insights from a P450 Carrier Protein complex reveal how specificity is achieved in the P450BioI ACP complex

Max J. Cryle, Ilme Schlichting

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120 Citations (Scopus)


Cytochrome P450BioI (CYP107H1) from the biotin operon of Bacillus subtilis forms a seven-carbon diacid through a multistep oxidative cleavage of a fatty acid linked to acyl carrier protein (ACP). Crystal structures of P450BioI in complex with three different length fatty acyl-ACP (Escherichia coli) ligands show that P450BioI binds the fatty acid such as to force the carbon chain into a U-shape above the active site heme. This positions the C7 and C8 carbons for oxidation, with a large additional cavity extending beyond the heme to accommodate the methyl termini of fatty acids beyond the site of cleavage. The structures explain the experimentally observed lack of stereo- and regiospecificity in the hydroxylation and cleavage of free fatty acids. The P450BioI-ACP complexes represent the only structurally characterized P450-carrier protein complexes to date, which has allowed the generation of a model of the interaction of the vancomycin biosynthetic P450 OxyB with its proposed carrier protein bound substrate.

Original languageEnglish
Pages (from-to)15696-15701
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number41
Publication statusPublished - 14 Oct 2008
Externally publishedYes


  • Acyl carrier protein
  • Biotin biosynthesis
  • Crystal structure
  • Cytochrome P450
  • Protein-protein interaction

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