Continuous transformation of chiral pharmaceuticals in enzymatic membrane bioreactors for advanced wastewater treatment

Abstract

This study demonstrates continuous enantiomeric inversion and further biotransformation of chiral profens including ibuprofen, naproxen and ketoprofen by an enzymatic membrane bioreactor (EMBR) dosed with laccase. The EMBR showed non-enantioselective transformations, with high and consistent transformation of both (R)- and (S)-ibuprofen (93 ± 6%, n = 10), but lower removals of both enantiomers of naproxen (46 ± 16%, n = 10) and ketoprofen (48 ± 17%, n = 10). Enantiomeric analysis revealed a bidirectional but uneven inversion of the profens, for example 14% inversion of (R)- to (S)- compared to 4% from (S)- to (R)-naproxen. With redox-mediator addition, the enzymatic chiral inversion of both (R)- and (S)-profens remained unchanged, although the overall conversion became enantioselective; except for (S)-naproxen, the addition of redox mediator promoted the degradation of (R)-profens only.

Robust biodegradation of naproxen and diclofenac by laccase immobilized using electrospun nanofibers with enhanced stability and reusability

“…After sampling, 0.1 mL of methanol was added prior to quantitative analysis. As naproxen is known for its resistance to enzymatic biodegradation [20] 0.1 mM of ABTS was added as a mediator agent to the solutions of that pharmaceutical.…”

“…The presence of the mediator is required to achieve satisfactory rates of reaction, as it is known that naproxen is insufficiently oxidized by the laccase and is resistant to enzymatic degradation [20]. The significant drop in the rates of degradation of both anti-inflammatory drugs at pH 7 is related to the formation of hydroxide ions, which can bind to the T2/T3 copper ions in the laccase structure.…”

Enantiospecific behaviour of chiral drugs in soil

“…Chiral inversion of S(+)-naproxen to R(-)-naproxen has been observed previously during wastewater treatment (Hashim et al, 2011;Suzuki et al, 2014). Furthermore, Nguyen et al (2017) reported bidirectional inversion of anti-inflammatories (naproxen, ibuprofen and ketoprofen) by an enzymatic membrane bioreactor. The results of the single enantiomer microcosms agree with those of the racemic microcosm whereby an enrichment of S(+)-naproxen was found (Figure 1).…”

“…Similarly, fungi such as Verticillium lecanii have been found to preferentially convert R(-)-ibuprofen to S(+)-ibuprofen by an enzymatic process related to mammalian studies (Thomason et al, 1998). However, evidence reporting the inversion of S(+)-ibuprofen to R(-)-ibuprofen by Nocardia bacteria exists (Mitsukura et al, 2002), as well as in lake water microcosms (Buser et al, 1999) and during wastewater treatment (Nguyen et al, 2017). The mechanism of chiral inversion remains poorly understood, particularly in the environment, but it is believed several enzymes play a role (Kato et al, 2003;Kato et al, 2004;Khan et al, 2014).…”

Analysis, fate and toxicity of chiral non-steroidal anti-inflammatory drugs in wastewaters and the environment: a review

“…Batch and flow through microcosm studies using spiked enantiomer concentrations enable a greater understanding of these processes whereby operational variables can be closely controlled. Several studies have reported limited or no enantioselectivity of ibuprofen in batch studies of diluted activated sludge (Escuder-Gilabert et al 2018) or laccase enzyme obtained from a culture of the white rot fungus Pleurotus ostreatus (Nguyen et al 2017). Furthermore, no enantioselectivity was observed in constructed wetlands treating synthetic or real wastewater under predominantly anaerobic conditions at dissolved oxygen concentrations less than 0.5 mg L −1 (Matamoros et al 2009).…”