Diversity of P450 redox systems and P450 fusion proteins. A selection of distinct
types of P450 enzymes and (where relevant) their redox partner systems is shown. The sizes of the
boxes are indicative of the lengths of the protein modules. Bound prosthetic groups
are indicated in the color-coded domains. A, P450BM-3 (CYP102A1)-type
P450-CPR fusion, also seen for fungal P450foxy (CYP505)-type systems (54). B, CYP116B-type P450-phthalate dioxygenase
reductase fusion (55). C, M.
capsulatus P450-FDx fusion CYP51FX (56).
D, R. rhodochrous P450-flavodoxin fusion XplA, involved in
reductive degradation of explosives (57). E,
Pseudomonas fluorescens PfO-1 acyl-CoA dehydrogenase-P450 fusion CYP222A1. This
protein is depicted with FAD bound in its N-terminal domain, but there is no report to date of
characterization of this protein. F, Mimivirus CYP5253A1, with a
P450 fused to a C-terminal domain of uncertain function but containing several potential sites for
post-translational modification. G, PpoA dioxygenase/peroxidase-P450 fusion enzyme
from A. nidulans, involved in Psi factor production (58). H, P450-hydrolase fusion CYP631B5, involved in mycophenolic
acid production (59). I,
“stand-alone” P450 that acts without partner proteins, typified by P450nor
(CYP55A)-type nitric-oxide reductase enzymes that interact directly with NAD(P)H, peroxygenase
CYP152 P450s that use H2O2 to oxidize substrates, P450s that isomerize
substrates (e.g. CYP5A1/8A1), and allene oxide synthase (CYP74A) dehydratase P450s.
J, typical eukaryotic Class II P450 systems with separate membrane-associated P450
and a CPR partner. K, Class I (mitochondrial) P450 system that interacts with the
iron-sulfur protein ADx, which is in turn reduced by ADR. Most bacterial systems use a similar redox
apparatus (60). L, variation on system K, in
which a flavodoxin replaces the iron-sulfur protein. This type of system supports CYP176A1
(P450cin); enables Citrobacter braakii to catabolize cineole; and can
also reduce CYP107H1 (P450BioI), involved in B. subtilis biotin
synthesis (61, 62).
M, heme-free EryCII P450-like protein devoid of a cysteine proximal ligand. EryCII
is an allosteric activator of the glycosyltransferase EryCIII in the production of erythromycin D in
S. erythraea (63).