*4.8. CYP Activity Titration with CYB5*

The CYB5 titration assay was performed in microplate format (96 wells) using the same enzyme assay conditions as described above (without NaCl), except substrate concentrations were hold constant (5 μM EthR, 20 μM coumarin or 7.5 μM DBF), applying a gradient of CYB5 (0–2000, 0–800 and 0–1000 nM for CYP1A2, 2A6 and 3A4, respectively).

**Supplementary Materials:** Supplementary materials can be found at http://www.mdpi.com/1422-0067/19/12/ 3914/s1.

**Author Contributions:** Conceptualization, M.K. and G.T.; methodology, D.C., B.C.G., B.B.P. and F.E.; formal analysis, M.K., G.T., T.L., P.U. and J.R.; writing—original draft preparation, D.C. and M.K.; writing—review and editing, all authors; project administration, M.K. and G.T.; funding acquisition, M.K. and G.T.

**Funding:** This work was in part financed by a joint project, funded by the Portuguese *Fundação para a Ciência e a Tecnologia* [Grant FCT-ANR/ BEXBCM/0002/2013, as well as Grant UID/BIM/0009/2016 of the Research Center for Toxicogenomics and Human Health (ToxOmics)] and the *L'Agence Nationale de la Recherche* [Grant ANR-13-ISV5-0001]. F.E. was supported with a post-doctoral fellowship grant of the Portuguese *Fundação para a Ciência e a Tecnologia* [Grant SFRH/BPD/110633/2015].

**Conflicts of Interest:** The authors declare no conflict of interest.
