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Review
. 2023 Dec 11;63(23):7299-7319.
doi: 10.1021/acs.jcim.3c01303. Epub 2023 Nov 19.

Mechanisms and Opportunities for Rational In Silico Design of Enzymes to Degrade Per- and Polyfluoroalkyl Substances (PFAS)

Melissa Marciesky  1 , Diana S Aga  2 , Ian M Bradley  3   4 , Nirupam Aich  5 , Carla Ng  1   6
Affiliations
Review

Mechanisms and Opportunities for Rational In Silico Design of Enzymes to Degrade Per- and Polyfluoroalkyl Substances (PFAS)

Melissa Marciesky et al. J Chem Inf Model. .

Abstract

Per and polyfluoroalkyl substances (PFAS) present a unique challenge to remediation techniques because their strong carbon-fluorine bonds make them difficult to degrade. This review explores the use of in silico enzymatic design as a potential PFAS degradation technique. The scope of the enzymes included is based on currently known PFAS degradation techniques, including chemical redox systems that have been studied for perfluorooctanesulfonic acid (PFOS) and perfluorooctanoic acid (PFOA) defluorination, such as those that incorporate hydrated electrons, sulfate, peroxide, and metal catalysts. Bioremediation techniques are also discussed, namely the laccase and horseradish peroxidase systems. The redox potential of known reactants and enzymatic radicals/metal-complexes are then considered and compared to potential enzymes for degrading PFAS. The molecular structure and reaction cycle of prospective enzymes are explored. Current knowledge and techniques of enzyme design, particularly radical-generating enzymes, and application are also discussed. Finally, potential routes for bioengineering enzymes to enable or enhance PFAS remediation are considered as well as the future outlook for computational exploration of enzymatic in situ bioremediation routes for these highly persistent and globally distributed contaminants.

Keywords: PFAS; bioremediation; contaminants; enzyme design.

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Conflict of interest statement

The authors declare no competing financial interest.

Figures

Figure 1
Figure 1
Possible route of degradation of PFOS (left) and PFOA (right) in aqueous solution with gamma irradation to generate hydrated electrons and hydroxyl radicals.,, The PFOS scheme was proposed to explain observed transformation products. Other reactions could continue the transformation process (for example, the PFOA product could enter cycle on the right) to result in further degradation.
Figure 2
Figure 2
Possible routes of degradation for PFOS (left) and PFOA (right) for a UV/persulfate system.,, Note that in this scheme degradation of PFOS yields PFOA, which can then enter the right-hand cycle.
Figure 3
Figure 3
Reaction cycle of HRP in the presence of a suitable substrate and H2O2 and without a substrate and excess H2O2. The black arrows represent the typical pathway, while the blue arrows represent other possible outcomes with excess H2O2 and no substrate present. The resting state of HRP is transformed to compound I through H2O2. Here the reaction can cycle to compound II or, if no substrate is present, can deactivate the enzyme (P670), return to the resting state, or form Compound II. Compound II will either return to the resting state (substrate/excess H2O2 pathway) or form Compound III if excess H2O2 is present. Compound III will then return to the resting state.,,
Figure 4
Figure 4
Molecular structure of cofactor B12. (A) The structure of B12 in the “base-on” form with cyanide (CN) as the R group, CN may be replaced with CH3 OH or 5′deoxyadenosyl. (B) B12 in the “base-on” form, top, and “base-off” form, bottom. (C) The structure of norpseudo-B12 in the “base-on” position.
Figure 5
Figure 5
Possible dehalogenation mechanism for PCeA for brominated phenols (top) and chloroethylenes (bottom). In the first step of the bromophenol (2,4,6-tribromophenol) pathway an electron is believed to be transferred from the super-reduced Co[I] to the ring. The substrate radical is neutralized and bromine is eliminated with another electron transfer from Co[I] or an iron–sulfur cluster. A proton can be provided from the upper cavity, from a Tyr residue (shown to lower left of the phenol), or from other solvent molecules. This process will continue until 2,4,6-tribomophenol is completely dehalogenated. In the dechlorination of chloroethylene (bottom row), the mechanism is believed to follow a heterolytic pathway.
Figure 6
Figure 6
(A) The binding of SAM in the active site of QueE to the iron–sulfur cluster (orange and yellow) with the magnesium(II) ion in proximity (blue atom). (B) The structure of AdoMet. (C) The mechanistic pathway of 7-carboxy-7-deaguanine synthase by the enzyme Que. Hydrogen abstraction is followed by radical rearrangement, which is facilitated by the magnesium ion.
Figure 7
Figure 7
Defluorination pathway of fluoroacetate by FAcD. In step one the SN2 reaction takes place defluorinating fluoroacetate. In step two, water hydrolyzes the ester intermediate.
Figure 8
Figure 8
Average energy barriers for 4 stages in the FAcD mechanism for fluoroaceate, difluoroacetate (S and R), and trifluoroacetate. Stage I: C–F activation, stage II: nucleophilic attack, stage III: C–O bond cleavage, and stage IV: proton transfer. These values come from the Supporting Information in Yue Y. et al. 2021.
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References

    1. Vidali M. Bioremediation. An overview. Pure Appl. Chem. 2001, 73 (7), 1163–1172. 10.1351/pac200173071163. - DOI
    1. Sharma B.; Dangi A. K.; Shukla P. Contemporary Enzyme Based Technologies for Bioremediation: A Review. J. Environ. Manage. 2018, 210, 10–22. 10.1016/j.jenvman.2017.12.075. - DOI - PubMed
    1. Kiss G.; Çelebi-Ölçüm N.; Moretti R.; Baker D.; Houk K. N. Computational Enzyme Design. Angew. Chem., Int. Ed. 2013, 52 (22), 5700–5725. 10.1002/anie.201204077. - DOI - PubMed
    1. Post G. B. Recent US State and Federal Drinking Water Guidelines for Per- and Polyfluoroalkyl Substances. Environ. Toxicol. Chem. 2021, 40 (3), 550–563. 10.1002/etc.4863. - DOI - PubMed
    1. Gluge J.; Scheringer M.; Cousins I. T.; DeWitt J. C.; Goldenman G.; Herzke D.; Lohmann R.; Ng C. A.; Trier X.; Wang Z. An Overview of the Uses of Per- and Polyfluoroalkyl Substances (PFAS). Environ. Sci. Process. Impacts 2020, 22 (12), 2345–2373. 10.1039/D0EM00291G. - DOI - PMC - PubMed

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