In Silico Identification of Bioremediation Potential: Carbamazepine and Other Recalcitrant Personal Care Products

Abstract

Emerging contaminants are principally personal care products not readily removed by conventional wastewater treatment and, with an increasing reliance on water recycling, become disseminated in drinking water supplies. Carbamazepine, a widely used neuroactive pharmaceutical, increasingly escapes wastewater treatment and is found in potable water. In this study, a mechanism is proposed by which carbamazepine resists biodegradation, and a previously unknown microbial biodegradation was predicted computationally. The prediction identified biphenyl dioxygenase from Paraburkholderia xenovorans LB400 as the best candidate enzyme for metabolizing carbamazepine. The rate of degradation described here is 40 times greater than the best reported rates. The metabolites cis-10,11-dihydroxy-10,11-dihydrocarbamazepine and cis-2,3-dihydroxy-2,3-dihydrocarbamazepine were demonstrated with the native organism and a recombinant host. The metabolites are considered nonharmful and mitigate the generation of carcinogenic acridine products known to form when advanced oxidation methods are used in water treatment. Other recalcitrant personal care products were subjected to prediction by the Pathway Prediction System and tested experimentally with P. xenovorans LB400. It was shown to biodegrade structurally diverse compounds. Predictions indicated hydrolase or oxygenase enzymes catalyzed the initial reactions. This study highlights the potential for using the growing body of enzyme-structural and genomic information with computational methods to rapidly identify enzymes and microorganisms that biodegrade emerging contaminants.

Carbamazepine biodegradation and volatile fatty acids production by selectively enriched sulfate‐reducing bacteria and fermentative acidogenic bacteria

“…Several compounds were generated, which could be attributed to CBZ planar conjugated p‐electron systems and the electronic configuration that enabled double bond formations 46 . Moreover, the oxidative transformation of CBZ by different microorganisms contributes significantly to CBZ biodegradation 47,48 . The anaerobic oxidation of hydrocarbons by SRB has also been documented 49,50 and agrees with the results of this study.…”

“…46 Moreover, the oxidative transformation of CBZ by different microorganisms contributes significantly to CBZ biodegradation. 47,48 The anaerobic oxidation of hydrocarbons by SRB has also been documented 49,50 and agrees with the results of this study. CBZ molecule oxidation may have initiated the main pathway and led to the formation of a radical CBZ cation (intermediate C), which, being unstable, further generated two isomers C1 (CBZOH, m/z = 253.0) and C2 (EPOCBZ, m/z = 253.0).…”

Poisson poisoning as the mechanism of action of the microtubule-targeting agent colchicine

“…To further explore this idea, we took advantage of the available structures of colchicine-bound tubulin (TC), unliganded soluble tubulin (Tub), and polymerized tubulin (Tubs) to quantify the accessibility of the binding channel of colchicine, as previously described (66). We used drug transport modeling method for colchicine transport because it has successfully predicted the transport of contaminants through several degradation enzymes (101), and ligand transport along hydrophobic enzymes (102), with binding channels similar to the hydrophobic binding pocket buried inside tubulin. Table 1 for the GTP-state tubulin, the average channel length varies significantly depending on the conformation of tubulin.…”

Bioremediation 3.0: Engineering pollutant-removing bacteria in the times of systemic biology

“…This latter information can be supplemented by the complementary prediction algorithm of a new public database RAPID (http://rapid.umn.edu/rapid/), currently being developed by the group of Lawrence P. Wackett at University of Minnesota. The idea of future utility of combined EAWAG-BBD and RAPID algorithms was provided recently by Aukema and co-workers who used these tools to predict initial metabolism of a set of emerging contaminants that include recalcitrant pharmaceuticals, alkyl phthalates, or fragrance compounds previously shown to be degraded by Paraburkholderia xenovorans LB400 (Aukema et al, 2016).…”

“…Indeed, the potential of in silico screening methods was demonstrated when investigating cytochrome P450-mediated metabolism of xenobiotics (Raunio et al, 2015). In a recent study by Aukema and colleagues, docking and molecular dynamics simulations allowed selection of biphenyl dioxygenase from Paraburkholderia xenovorans LB400 as the best candidate enzyme for metabolizing carbamazepine, one of the most commonly identified recalcitrant pharmaceuticals in rivers (Aukema et al, 2016). The…”