Deciphering the N1-substituent effects on biodegradation of sulfonamides: Novel insights revealed from molecular biology and computational chemistry approaches

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 N¹-substituent rings. Despite structural variations, all sulfonamides follow a consistent degradation pathway, yielding aminated heterocycles as end products. This pathway involves key steps such as dehydrogenation activation, ipso-hydroxylation, and the cleavage of S-N and S-C bonds, with the latter being particularly influenced by the N¹-substituents. Heterocyclic structures affect biodegradation rates by altering the electronic density at the C³ and N¹ atoms of sulfonamides. Substituents with higher electron-donating potential and lower Gibbs free energy barriers for S-C and C-N bond cleavage significantly enhance biodegradation efficiency. This work not only deciphers the universal biodegradation mechanism of sulfonamides but also offers theoretical insights for predicting the biodegradation behavior and pattern of emerging contaminants. These findings contribute to the effective removal of emerging contaminants from aquatic environments, advancing the practical application of biotreatment technologies.