Transformation of ibuprofen by Bacillus megaterium – Reversible glycosylation of the unhydroxylated drug and generation of hydroxylated and conjugated metabolites

ABSTRACT: Several pharmaceuticals persist in wastewater plants and contaminate increasingly natural water bodies, even ground water. In this study, different bacteria with known capabilities to degrade aromatic environmental pollutants – belonging to the genera Bacillus, Paenibacillus, Mycobacterium and Cupriavidus - were screened for their ability to transform the anti-inflammatory drug ibuprofen. Bacillus megaterium SBUG 518 as one of the most efficient strains tested was almost completely inhibited by 0.05% ibuprofen at pH 6 but was able to transform 0.005% ibuprofen within 4 h up to 92%. Four products were identified by HPLC and LC/MS. The drug was transformed via three different biotransformation reactions involving (A) conjugate formation of ibuprofen with a sugar molecule (B) the hydroxylation of the isobutyl side chain at two positions, and (C) glycosylation of 2-hydroxyibuprofen. The ibuprofen conjugate (ibuprofen pyranoside) was considerably less toxic to B. megaterium than the parent compound. Its reversible formation can lead to a temporary remarkable underestimation of ibuprofen concentrations in environmental “elimination” studies. Proteomic analyses including 1264 identified proteins suggest that cytochrome P450 BM3 plays a pivotal role in ibuprofen hydroxylation. Additionally, several proteins involved in stress response as well as proteins with similarity to multidrug efflux pump proteins were found in higher abundance in ibuprofen-incubated bacteria.

INSTRUMENT(S):

ORGANISM(S): Bacillus Megaterium

SUBMITTER: Tjorven Hinzke  

LAB HEAD: Katharina Riedel

PROVIDER: PXD015716 | Pride | 2025-04-14

REPOSITORIES: Pride