Scytalidium thermophilum produces a catalase with phenol oxidase activity (CATPO) that catalyses the dismutation of hydrogen peroxide (H2O2) to dioxygen and water and also oxidizes several phenolic compounds in the absence of hydrogen peroxide. It comprises 717 amino acids with a 19 amino acid signal sequence, and a 17 amino acid prosequence. It is a homotetrameric protein of molecular mass 320 kDa and subunit molecular mass 80 kDa. Although catalases have been studied for many years, a peroxide independent oxidative activity of catalases has recently been recognized. There are a great number of reports available describing the structural and biochemical characterization of catalases. However basic questions related to substrate and product flow remain unanswered, particularly related to the oxidase activity. The goals of our current studies are to investigate the main and lateral channels known that connect the deeply buried active site to the exterior of the enzyme. We have introduced a number of mutations into these regions and analyzed their specific activities. (C) 2015 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY-NC-ND license.