Adaptive genetic trade-offs govern the enantioselective degradation and horizontal transfer of ibuprofen catabolic genes.

Ibuprofen (IBU), a prevalent chiral pharmaceutical, was a common emerging contaminant in municipal wastewater. The mechanisms underlying its enantioselective microbial degradation and the horizontal gene transfer (HGT) of associated ipf genes remain poorly understood. Here, we reported Sphingopyxis sp. 550A, a bacterium capable of degrading both IBU enantiomers but exhibited a distinct preference for R-(-)-IBU, which preference was determined by the IpfF, an aromatic CoA ligase. Molecule docking analysis revealed that differential catalytic atomic distances govern enantioselective efficiency of IpfF. The ipfABDEFG genes demonstrated concentration-dependent genetic dynamics: low IBU stress (1 mg·L-1) promoted ipfABDEFG gene cluster transfer to other sphingomonads through HGT, while high stress (≥ 10 mg·L-1) induced toxic intermediate accumulation and IS6100-mediated gene loss to alleviate cellular toxicity. Leveraging these insights, we constructed a microbial co-culture of strain 550 A and Pseudomonas putida KT2440 for complete removal of high-concentration IBU and its toxic metabolite, 4-isobutylcatechol. This work provided a framework for understanding enzymatic enantioselectivity toward chiral pharmaceuticals and highlights the role of HGT in shaping bioremediation potential within engineered microbial communities.