Hydroxylation of flavanones by cytochrome P450 105D7 from Streptomyces avermitilis

• CYP105D7 catalyzes hydroxylation of two flavanones, naringenin and pinocembrin.
• CYP105D7 binds to naringenin and pinocembrin in a weakly cooperative manner.
• A possible binding model of naringenin was investigated by molecular-docking analyses.

Flavanones have a wide range of pharmacological activities. Previously, we showed that CYP105D7, a cytochrome P450, from Streptomyces avermitilis can catalyze hydroxylation of diclofenac at the C4′ position. Here, we demonstrated that CYP105D7 also catalyzes hydroxylation of two flavanones, naringenin and pinocembrin. Naringenin was hydroxylated at the 3′-position in a regiospecific manner to yield eriodictyol. Spectroscopic analyses showed that CYP105D7 binds to naringenin and pinocembrin in a weakly cooperative manner with an affinity of 103 μM and 52 μM, and a Hill coefficient of 1.25 and 1.47, respectively. A possible binding model of naringenin was investigated by molecular-docking analyses. The substrate-binding pocket of CYP105D7 is sufficiently wide to accommodate two naringenin molecules simultaneously, and the C3′ atom of the proximal molecule is in the appropriate location for aromatic hydroxylation.

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