Exploring hitherto uninvestigated reactions of the fatty acid peroxygenase CYP152A1: catalase reaction and Compound I formation†

Abstract

CYP152A1 (cytochrome P450_BSβ) is a fatty acid peroxygenase, which specifically catalyses the oxidation of long-chain fatty acids using hydrogen peroxide as an oxidant. We have found that CYP152A1 possesses catalase activity, which competes with the hydroxylation of long-chain fatty acids, the oxidation of non-native substrates, and haem degradation. Using hydrogen peroxide, Compound I of CYP152A1 could not be observed, due to its swift decomposition via catalase activity, where Compound I reacts with another molecule of hydrogen peroxide to form O₂. In contrast, a clear spectral change indicative of Compound I formation was observed when mCPBA was employed as the oxidant. This work presents valuable insights into an important role for the catalase activity of CYP152A1 in avoiding enzyme deactivation when no substrate is available for oxidation.