Conservation and cloning of CYP51: a sterol 14 alpha-demethylase from Mycobacterium smegmatis

Colin J. Jackson, David Christopher Lamb, Timothy H. Marczylo, Josie E. Parker, Nigel L. Manning, Diane Elizabeth Kelly, Steven Lewis Kelly

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36 Citations (SciVal)

Abstract

The genetic locus encoding cytochrome P450 51 (CYP51; P45014DM) in Mycobacterium smegmatis is described here together with confirmation of activity in lanosterol 14α-demethylation. The protein bound azole antifungals with high affinity and the rank order based on affinity matched the ranked order for microbiological sensitivity of the organism, thus supporting a possible role for CYP51 as a target in the antimycobacterial activity of these compounds. Non-saponifiable lipids were extracted from the bacteria grown on minimal medium. Unlike a previous report using growth on complex medium, no cholesterol was detected in two strains of M. smegmatis, but a novel lipid was detected. The genetic locus of CYP51 is discussed in relation to function; it is conserved as part of a putative operon in M. smegmatis, Mycobacterium tuberculosis, Mycobacterium avium, and Mycobacterium bovis and consists of six open-reading frames including two CYPs and a ferredoxin under a putative Tet-R regulated promoter.
Original languageEnglish
Pages (from-to)558-563
Number of pages6
JournalBiochemical and Biophysical Research Communications
Volume301
Issue number2
Early online date15 Jan 2003
DOIs
Publication statusPublished - 07 Feb 2003

Keywords

  • cytochrome P450
  • Sterol 14-demethylase
  • Azole
  • Mycobacteria

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