MT FdR:: a ferredoxin reductase from M-tuberculosis that couples to MT CYP51

We report the molecular cloning, expression and partial characterization of MT FdR, an FAD-associated flavoprotein, from Mycobacterium tuberculosis similar to the oxygenase-coupled NADH-dependent ferredoxin reductases (ONFR). We establish, through kinetic and spectral analysis, that NIT FdR preferentially uses NADH as cofactor. Furthermore, MT FdR forms a complex with mycobacterial ferredoxin (NIT Fdx) and NIT CYP51, a cytochrome P450 (CYP) from M. tuberculosis that is similar to lanosterol 14 alpha-demethylase isozymes. This reconstituted system transfers electrons from the cofactor to the heme iron of NIT CYP51 and effects the demethylation of lanosterol. (c) 2004 Elsevier B.V. All rights reserved.