Bacterial cytochromes P‐450

Abstract

The cytochromes P-450 (P-450s) constitute an extremely large family ('superfamily') of haemoproteins that catalyse the oxidation of a wide range of physiological and non-physiological compounds. A remarkable feature of the P-450s is the manipulation of the same basic structure and chemistry to achieve an enormous range of functions in organisms as diverse as bacteria and man. Indeed, the P-450s have been described as 'the most versatile biological catalyst known'. Much research is focussed on mammalian P-450s, with their roles in such processes as steroid transformations and the metabolism of carcinogens and other xenobiotics. However, our knowledge of the structure and function of the P-450s has been advanced by analysis of a limited number of its bacterial members, primarily P-450cam from Pseudomonas putida. Four P-450 structures have been solved to date, all of which are from bacterial sources. The aim of this review is to assess current knowledge of the many bacterial P-450s, with emphasis on their diverse biological roles and on the advances in our knowledge of this extremely important enzyme class, which have been made feasible through their study.

Comparative and functional genomics of the Mycobacterium tuberculosis complex a aThis review is based on the 2002 Marjory Stephenson Prize Lecture delivered by the author at the 150th Meeting of the Society for General Microbiology, 9 April 2002.

“…Secondly, there are 20 enzyme systems that are predicted to use cytochrome P450 as a cofactor and these are often involved in the degradation of xenobiotics, or the modification of organic molecules, such as sterols, by means of their mono-oxygenase activity (Aoyama et al, 1998). These enzymes are common in soil organisms where they enable diverse organic matter to be degraded to yield metabolizable sources of carbon and energy (Aoyama et al, 1998 ;Munro & Lindsay, 1996). Both the regulatory networks and the P450 systems have been subject to massive gene decay in M. leprae (Cole et al, 2001 ;Eiglmeier et al, 2001).…”

Unusual Spectroscopic and Ligand Binding Properties of the Cytochrome P450-Flavodoxin Fusion Enzyme XplA

“…In bacterial P450 systems, these are often soluble NAD(P)H-dependent ferredoxin reductase and iron-sulfur ferredoxin proteins. This is a so-called class I P450 redox system, analogous to the adrenodoxin reductase/ adrenodoxin system responsible for driving steroidogenic P450s in eukaryotic mitochondria (17,18). However, the majority of mammalian and other eukaryotic P450s receive electrons from the diflavin enzyme NADPH-cytochrome P450 reductase in a membrane-associated class II redox system (16,17).…”

Flavocytochrome P450 BM3 Mutant A264E Undergoes Substrate-dependent Formation of a Novel Heme Iron Ligand Set

“…The source of the electron is reduced pyridine nucleotides (NADPH or NADH), and electron transfer is usually mediated by one or more redox partner enzymes. In hepatic P450 systems, the redox partner is the NADPH-dependent diflavin-cytochrome P450 reductase, which contains FAD and FMN cofactors (1,5). In mammalian adrenal systems and many bacterial P450 enzymes, electrons are delivered via a two-protein redox system comprising an FAD-containing reductase (adrenodoxin reductase or ferredoxin reductase) and an iron-sulfur protein (ferredoxin) (6,7).…”