Fatty acid signals in Bacillus megaterium are attenuated by cytochrome P-450-mediated hydroxylation

Neil English, Colin N.A. Palmer, William L. Alworth, Lan Kang, Valerie Hughes, C. Roland Wolf

    Research output: Contribution to journalArticlepeer-review

    22 Citations (Scopus)

    Abstract

    In previous publications we have demonstrated that peroxisome proliferators and non-steroidal anti-inflammatory drugs are inducers of the cytochrome P-450(BM-3) gene in Bacillus megaterium ATCC14581. Their mechanism of action involves binding to and subsequent displacement of the transcriptional repressor, Bm3R1, from its operator site, which results in the activation of cytochrome P-450(BM-3) gene transcription. We now present evidence that the branched-chain fatty acid, phytanic acid, is a potent inducer of cytochrome P-450(BM-3). We have also observed that phytanic acid and peroxisome proliferators are inducers of Bm3R1 protein accumulation and associated DNA-binding activity. In contrast, several barbiturates, although capable of inducing cytochrome P-450(BM-3) and Bm3R1 gene transcription, were unable to induce the Bm3R1 protein. We also demonstrate that cytochrome P-450(BM-3) readily oxidizes phytanic acid, and provide evidence that, although the ω-1 hydroxy acid derivatives of phytanic acid can associate with Bm3R1, they do so with an affinity two orders of magnitude lower than the unmodified fatty acid. As a consequence, the ability of the hydroxylated product to induce cytochrome P-450(BM-3) gene expression in vivo is markedly reduced. These data collectively suggest that metabolism of fatty acids by cytochrome P-450 leads to an attenuation of their ability to activate the transcription of the BM-3 operon. This work places the action of bacterial fatty acid hydroxylases in an autoregulatory loop where they may be responsible for the inactivation or clearance of the inducing fatty acid signal.

    Original languageEnglish
    Pages (from-to)363-368
    Number of pages6
    JournalBiochemical Journal
    Volume327
    Issue number2
    DOIs
    Publication statusPublished - 15 Oct 1997

    Fingerprint

    Dive into the research topics of 'Fatty acid signals in Bacillus megaterium are attenuated by cytochrome P-450-mediated hydroxylation'. Together they form a unique fingerprint.

    Cite this