<p>Biological methane oxidation stands as an exceptionally coveted method for transforming natural gas into a liquid state, meeting the burgeoning demands for fuel and chemical feedstock while concurrently alleviating the potent greenhouse effects associated with methane emissions. The longstanding presumption, owing to the absence of naturally occurring hemoenzymes capable of catalyzing methane-to-methanol conversion, posited that hemoenzymes, including cytochrome P450s (P450s), were inept at facilitating the oxidative conversion of methane. In a groundbreaking revelation, we now report the catalytic oxidation of methane by wild-type P450BM3, achieved without resorting to any mutagenesis, under the influence of chemically evolved dummy substrates (decoy molecules) at high-pressure methane conditions of 10 MPa. Our comprehensive investigations unfold a compelling narrative wherein methane undergoes catalytic conversion into methanol at ambient temperatures, showcasing a remarkable total turnover number of 4.0±0.4. This discovery not only challenges the previously held beliefs regarding the catalytic potential of hemoenzymes but also opens new avenues for advancing our understanding of methane transformation processes. In essence, this breakthrough holds promise for addressing the dual imperatives of sustainable energy production and environmental stewardship, marking a pivotal stride in the ongoing quest for innovative solutions to pressing global challenges.</p>