Spectroscopic studies of the interaction between phosphorus heterocycles and cytochrome P450

Dumei Ma; Libo Zhang; Yingwu Yin; Yuxing Gao; Qian Wang

doi:10.1016/j.jpha.2020.12.004

Spectroscopic studies of the interaction between phosphorus heterocycles and cytochrome P450

J Pharm Anal. 2021 Dec;11(6):757-763. doi: 10.1016/j.jpha.2020.12.004. Epub 2020 Dec 21.

Authors

Dumei Ma^{1

2}, Libo Zhang², Yingwu Yin¹, Yuxing Gao³, Qian Wang²

Affiliations

¹ Department of Chemical and Biochemical Engineering, College of Chemistry and Chemical Engineering, Xiamen University, Xiamen, 361005, Fujian, China.
² Department of Chemistry and Biochemistry, University of South Carolina, Columbia, SC, 29208, USA.
³ Department of Chemistry and Key Laboratory for Chemical Biology of Fujian Province, College of Chemistry and Chemical Engineering, Xiamen University, Xiamen, 361005, Fujian, China.

Abstract

P450 fatty acid decarboxylase OleT from Staphylococcus aureus (OleT_SA) is a novel cytochrome P450 enzyme that catalyzes the oxidative decarboxylation of fatty acids to yield primarily terminal alkenes and CO₂ or minor α- and β-hydroxylated fatty acids as side-products. In this work, the interactions between a series of cycloalkyl phosphorus heterocycles (CPHs) and OleT_SA were investigated in detail by fluorescence titration experiment, ultraviolet-visible (UV-vis) and ³¹P NMR spectroscopies. Fluorescence titration experiment results clearly showed that a dynamic quenching occurred when CPH-6, a representative CPHs, interacted with OleT_SA with a binding constant value of 15.2 × 10⁴ M^-1 at 293 K. The thermodynamic parameters (ΔH, ΔS and ΔG) showed that the hydrogen bond and van der Waals force played major roles in the interaction between OleT_SA and CPHs. The UV-vis and ³¹P NMR studies indicated the penetration of CPH-6 into the interior environment of OleT_SA, which greatly affects the enzymatic activity of OleT_SA. Therefore, our study revealed an effective way to use phosphorus heterocyclic compounds to modulate the activity of cytochrome P450 enzymes.

Keywords: Cytochrome P450; Interaction; OleT; Phosphorus heterocycles; Spectroscopy.