The wide abundance and its high H/C ratio make methane an ideal bridge to lower the carbon footprint of energy carriers and chemicals. Using our biochemistry-inspired approach, we propose a program for converting methane to methanol under mild conditions using O2 as oxidant. We base our proposal on promising results using a Cu-based zeolite to selectively oxidize methane. It is the central hypothesis that the zeolite pores offer a unique environment, which stabilizes tailored transition metal oxide clusters that react selectively with methane, but do not oxidize methanol further. This selectivity is to be achieved by adjusting the redox potential and Lewis acidity of the clusters such that the hydrogen abstraction from methanol is not favored. The key challenge will be to understand and manipulate the reaction pathway in order to be able to operate under conditions that allow stabilization of the metal oxide cluster also in the presence of water formed during the reaction. The project tightly links theoretical and experimental research to design and realize new active and selective methane oxidation catalysts based on zeolite metal oxide host-guest systems. We will explore the impact of the steric environment and polarity of the zeolite environment and the redox nature of the metal oxide cluster (e.g., with Cu, Fe, Co, and Ni). Theory of catalytic methane oxidation will be used to rationalize the experimental observations and at the same time provide guidance to the experimental research.