Cytochromes P450 monooxygenases

Cytochrome P450 monooxygenases are characterized through the presence of the heme (protoporphyrin IX) prosthetic group (Scheme 10.1) that is coordinated to the enzyme through a conserved cysteine ligand. They have obtained their name from the signature absorption band with a maximum near 450 nm in the difference spectrum when incubated with CO. The absorption arises from the Soret Jilt transition of the ferrous protoporphyrin IX-CO complex. 

Scheme 10.3 Electron-transport systems associated with cytochrome P450 monooxygenases. Arrows indicate electron transfer.

Williams PA, Cosme J, Sridhar V, Johnson EF, McRee DE. Mammalian microsomal cytochrome P450 monooxygenase structural adaptations for membrane binding and functional diversity. Mol Cell 2000 5 121-31. 

This can be degraded by several mycobacteria including Mycobacterium aurum strain MOl (Combourieu et al. 1998), Mycobacterium strain RPl (Poupin et al. 1998), and Mycobacterium chelonae (Swain et al. 1991). The reaction is initiated by a cytochrome P450 monooxygenase that is also active against pyrrolidine and piperidine (Poupin et al. 1998). 

Circulating melatonin is metabolized mainly in the liver, where it is first hydroxylated in the C6-position by cytochrome P450 monooxygenases (isoenzymes... 

Cashman, J.R. (2005) Some distinctions between flavin-containing and cytochrome P450 monooxygenases. Biochemical and Biophysical Research Communications, 338, 599-604. 

Cytochrome P450 monooxygenases (P450s) have significant potential in biotransformation applications because their ability to insert molecular oxygen regiospecifically and... 

Urlacher, V.B. and Eiben, S. (2006) Cytochrome P450 monooxygenases perspectives for synthetic application. 

Fig. 22.3 Cytochrome P450 monooxygenases and nicotine metabolism. An alignment of the amino acid sequences of the enzymes 2A6 and 2D6. Occurrences of the same amino acid residue at the same position are shown in black. Putative substrate recognition sites (SRS1—...

SCHULER, M.A., Plant cytochrome P450 monooxygenases, Crit. Rev. in Plant Sci., 1996,15,235-284. 

OTANI, K., TAKAHASHI, T., FURUYA, T., AYABE, S., Licondione synthase, a cytochrome P450 monooxygenase catalyzing 2-hydroxylation of 5-deoxyflavanone, in cultured Glycyrrhiza enchinata L. cells, Plant Physiol., 1994,105,1427-1432. 

BERTEA, C.M., SCHALK, M KARP, F., MAFFEI, M CROTEAU, R., Demonstration that menthofuran synthase of mint (Mentha) is a cytochrome P450 monooxygenase cloning, functional expression, and characterization of the responsible gene, Arch. Biochem. Biophys., 2001,390,279-286. 

---