Heme dioxygenases

The heme dioxygenase enzymes involved in tryptophan oxidation catalyse the first and rate-limiting step in the kynurenine pathway—the 02-dependent oxidation of 1-tryptophan to AT -formylkynurenine. In the past 10 years, there have been substantial new developments, including new structural information, bacterial expression systems for a number of dioxygenases, contributions from computational chemistry, and emerging... 

Scheme 1. The reaction catalyzed by the heme dioxygenase enzymes.

Scheme 3. Previous proposals (5,21,49) for the reaction mechanism in the heme dioxygenases via either Criegee (blue) or dioxetane (red) pathways.

Scheme 4. The variously proposed alternative reaction mechanisms for heme dioxygenases, (a) The base-catalyzed abstraction mechanism (21,49). (b) An alternative to the base-catalyzed mechanism, using proton abstraction by the bound O2 (23,27). (c) Electrophilic addition (31,50,51). (d) Radical addition (50-53). The majority opinion from crystallography (27), mass spectrometry (30), mutagenesis (54), and computational work (50) concludes that (a) and (b) are unlikely. It is not yet known whether addition at C or is most likely both have been suggested (31,50-53,55).

Brodhun F, Gobel C, Hornung E, Feussner I (2009) Identification of PpoA from Aspergillus nidulans as a fusion protein of a fatty acid heme dioxygenase/ peroxidase and a cytochrome P450. J Biol Chem 284 11792-11805... 

Seo J, Kang S-I, Kim M, Han J, Hur H-G (2011) Flavonoids biotransformation by bacterial non-heme dioxygenases, biphenyl and naphthalene dioxygenase. Appl Microbiol Biotechnol 91 219-228... 

---