TY - JOUR
T1 - Conservation and cloning of CYP51: a sterol 14 alpha-demethylase from Mycobacterium smegmatis
AU - Jackson, Colin J.
AU - Lamb, David Christopher
AU - Marczylo, Timothy H.
AU - Parker, Josie E.
AU - Manning, Nigel L.
AU - Kelly, Diane Elizabeth
AU - Kelly, Steven Lewis
N1 - Jackson, C. J., Lamb, D. C., Marczylo, T. H., Parker, J. E., Manning, N. L., Kelly, D. E., Kelly, S. L. (2003). Conservation and cloning of CYP51: a sterol 14 alpha-demethylase from Mycobacterium smegmatis. Biochemical and Biophysical Research Communications, 30301, (2), 558-563.
Sponsorship: BBSRC
PY - 2003/2/7
Y1 - 2003/2/7
N2 - 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.
AB - 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.
KW - cytochrome P450
KW - Sterol 14-demethylase
KW - Azole
KW - Mycobacteria
U2 - 10.1016/S0006-291X(02)03078-4
DO - 10.1016/S0006-291X(02)03078-4
M3 - Article
SN - 0006-291X
VL - 301
SP - 558
EP - 563
JO - Biochemical and Biophysical Research Communications
JF - Biochemical and Biophysical Research Communications
IS - 2
ER -
