Laccase‐Based Self‐Amplifying Catalytic System Enables Efficient Antibiotic Degradation for Sustainable Environmental Remediation

Antibiotic contamination poses potential risks to ecosystems and human health. Laccase (LAC) has emerged as a promising biocatalyst for the oxidation of environmentally toxic contaminants with high catalytic efficiency; however, its large‐scale application is hindered by enzyme costs and dependency on redox mediators. Herein, a novel self‐amplifying catalytic system (SACS) for antibiotic remediation that does not require external mediators is developed. In SACS, a natural mediator‐regenerating koji with high‐activity LAC, derived from lignocellulosic waste, initiates the chlortetracycline (CTC) degradation. Subsequently, an intermediate product, CTC327, identified as an active mediator for LAC via molecular docking, is formed and then starts a renewable reaction cycle, including CTC327‐LAC interaction, stimulated CTC bioconversion, and self‐amplifying CTC327 release, thus enabling highly efficient antibiotic bioremediation. In addition, SACS exhibits excellent performance in producing lignocellulose‐degrading enzymes, highlighting its potential for lignocellulosic biomass deconstruction. To demonstrate its effectiveness and accessibility in the natural environment, SACS is used to catalyze in situ soil bioremediation and straw degradation. The resulting CTC degradation rate is 93.43%, with a straw mass loss of up to 58.35% in a coupled process. This mediator regeneration and waste‐to‐resource conversion in SACS provides a promising route for environmental remediation and sustainable agricultural practices.