The first crystal structure of a class VII P450, CYP1161346 from Tepidiphilus thermophilus, has been solved at 1.9 angstrom resolution. The structure reveals overall conservation of the P450-fold and a water conduit around the I-helix. Active site residues have been identified and sequence comparisons have been made with other class VII enzymes. A structure similarity search demonstrated that the P450-TT structure is similar to enzymes capable of oxy-functionalization of fatty acids, terpenes, macrolides, steroids and statins. The insight gained from solving this structure will provide a guideline for future engineering and modelling studies on this catalytically promiscuous class of enzymes. (C) 2018 Elsevier Inc. All rights reserved.