9.B.470.  The Flavin-containing MonoOxygenase 2 (FMO2) Family  

FMO2 catalyzes the oxidative metabolism of numerous xenobiotics, including mainly therapeutic drugs and insecticides that contain a soft nucleophile, most commonly nitrogen or sulfur and participates to their bioactivation (Francois et al. 2009). It specifically catalyzes S-oxygenation of sulfur derived compounds such as thiourea-derived compounds, thioetherorganophosphates to their sulfenic acid (Henderson et al. 2004).  In vitro, it catalyzes S-oxygenation of the second-line antitubercular drugs thiacetazone (TAZ) and ethionamide (ETA), forming a sulfinic acid and a carbodiimide via a postulated sulfenic acid intermediate (Francois et al. 2009).  It also catalyzes S-oxygenation of the thioether-containing organophosphate insecticides, phorate and disulfoton and prevents pathological cardiac hypertrophy by maintaining the ER-mitochondria association through interaction with the IP3R2-Grp75-VDAC1 complex ().Xiao et al. 2025


 

References:

Francois, A.A., C.R. Nishida, P.R. de Montellano, I.R. Phillips, and E.A. Shephard. (2009). Human flavin-containing monooxygenase 2.1 catalyzes oxygenation of the antitubercular drugs thiacetazone and ethionamide. Drug Metab Dispos 37: 178-186.
Henderson, M.C., S.K. Krueger, J.F. Stevens, and D.E. Williams. (2004). Human flavin-containing monooxygenase form 2 S-oxygenation: sulfenic acid formation from thioureas and oxidation of glutathione. Chem Res Toxicol 17: 633-640.
Xiao, C., C. Wang, J. Wang, X. Wu, C. Ke, J. Nan, H. Ding, Y. Xu, Y. Shi, J. Zhao, C. Ni, Q. Liu, J. Li, S. Sheng, H. Chen, J. Cai, T. Zhao, J. Chen, Q. Sun, B. Zhou, J. Wang, W. Zhu, and X. Hu. (2025). FMO2 Prevents Pathological Cardiac Hypertrophy by Maintaining the ER-Mitochondria Association Through Interaction With IP3R2-Grp75-VDAC1. Circulation 151: 1667-1685.
Examples:

TC#NameOrganismal TypeExample
9.B.470.1.1

Flavin-containing monooxygenase 2, FMO2, of 535 aas and 2 TMSs, one N-terminal and one C-terminal. (See family description for a fairly detailed description of this enyme.)

FMO2 of Homo sapiens

 
9.B.470.1.2

Flavin monooxidase, Fmo5, of 537 aas and 2 TMSs, one N-terminal and one C-terminal.

Fmo5 of Xenopus tropicalis (Western clawed frog) (Silurana tropicalis)

 
9.B.470.1.3

Flavin monooxidase of 578 aas and 2 TMSs, N- and C-terminal.

FMO of Sus scrofa (pig)