Through surveying a highly diverse set of laccases we have elucidated that AFB1 degradation activity is widespread and have identified specific clades to target for future optimization effort. In addition, we propose a reaction scheme that would explain the process through which AFB1 is oxidized to AFQ1. In our proposed reaction, the carbons with the highest spin densities are the ideal sites to pair with external single electron donors and these optimal carbons were used to perform docking simulations. Based on our experimental and computational results we predicted that active site shape and the positioning of AFB1's key, high-spin-density carbons can have a significant impact on enzyme efficiency, an important piece of information to be used in future efforts to understand of laccases' ability to decontaminate AFB1. These elements create a foundation of which the field can further advance efforts in developing efficient and effective approaches for detoxifying AFB1, improving the metabolic health of billions of people around the globe.