Elucidating biodegradation mechanisms and predicting pollutant reactivities are essential for advancing the application of biodegradation engineering to address the challenge of thousands of emerging contaminants. Molecular biology and computational chemistry are powerful tools for this purpose, enabling the investigation of biochemical reactions at both the gene and atomic levels. This study employs the biodegradation of ten sulfonamide antibiotics as a case study to demonstrate the integration of genomics and quantum chemistry approaches in exploring the biodegradation behavior of emerging contaminants. The isolated functional strain, Paenarthrobacter sp., could completely degrade all ten model sulfonamides under aerobic conditions. These compounds share a 4-aminobenzenesulfonamide core but differ in N