Synthesis and enzymatic ketonization of the 5-(halo)-2-hydroxymuconates and 5-(halo)-2-hydroxy-2,4-pentadienoates
5-Halo-2-hydroxymuconates and 5-halo-2-hydroxy-2,4-pentadienoates are stable dienols that are proposed intermediates in bacterial meta-fission pathways for the degradation of halogenated aromatic compounds. The presence of the halogen raises questions about how the bulk and/or electronegativity of t...
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| Format: | Article |
| Language: | English |
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Beilstein-Institut
2017-05-01
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| Series: | Beilstein Journal of Organic Chemistry |
| Subjects: | |
| Online Access: | https://doi.org/10.3762/bjoc.13.101 |
| _version_ | 1818918072257347584 |
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| author | Tyler M. M. Stack William H. Johnson Jr. Christian P. Whitman |
| author_facet | Tyler M. M. Stack William H. Johnson Jr. Christian P. Whitman |
| author_sort | Tyler M. M. Stack |
| collection | DOAJ |
| description | 5-Halo-2-hydroxymuconates and 5-halo-2-hydroxy-2,4-pentadienoates are stable dienols that are proposed intermediates in bacterial meta-fission pathways for the degradation of halogenated aromatic compounds. The presence of the halogen raises questions about how the bulk and/or electronegativity of these substrates would affect enzyme catalysis or whether some pathway enzymes have evolved to accommodate it. To address these questions, 5-halo-2-hydroxymuconates and 5-halo-2-hydroxy-2,4-pentadienoates (5-halo = Cl, Br, F) were synthesized and a preliminary analysis of their enzymatic properties carried out. In aqueous buffer, 5-halo-2-hydroxy-2,4-pentadienoates rapidly equilibrate with the β,γ-unsaturated ketones. For the 5-chloro and 5-bromo derivatives, a slower conversion to the α,β-isomers follows. There is no detectable formation of the α,β-isomer for the 5-fluoro derivative. Kinetic parameters were also obtained for both sets of compounds in the presence of 4-oxalocrotonate tautomerase (4-OT) from Pseudomonas putida mt-2 and Leptothrix cholodnii SP-6. For 5-halo-2-hydroxymuconates, there are no major differences in the kinetic parameters for the two enzymes (following the formation of the β,γ-unsaturated ketones). In contrast, the L. cholodnii SP-6 4-OT is ≈10-fold less efficient than the P. putida mt-2 4-OT in the formation of the β,γ-unsaturated ketones and the α,β-isomers from the 5-halo-2-hydroxy-2,4-pentadienoates. The implications of these findings are discussed. The availability of these compounds will facilitate future studies of the haloaromatic catabolic pathways. |
| first_indexed | 2024-12-20T00:44:09Z |
| format | Article |
| id | doaj.art-38aa5f36456b4a94b022769732709965 |
| institution | Directory Open Access Journal |
| issn | 1860-5397 |
| language | English |
| last_indexed | 2024-12-20T00:44:09Z |
| publishDate | 2017-05-01 |
| publisher | Beilstein-Institut |
| record_format | Article |
| series | Beilstein Journal of Organic Chemistry |
| spelling | doaj.art-38aa5f36456b4a94b0227697327099652022-12-21T19:59:27ZengBeilstein-InstitutBeilstein Journal of Organic Chemistry1860-53972017-05-011311022103110.3762/bjoc.13.1011860-5397-13-101Synthesis and enzymatic ketonization of the 5-(halo)-2-hydroxymuconates and 5-(halo)-2-hydroxy-2,4-pentadienoatesTyler M. M. Stack0William H. Johnson Jr.1Christian P. Whitman2Department of Molecular Biosciences, College of Natural Sciences, 1 University Station, University of Texas, Austin, TX 78712, USADivision of Chemical Biology and Medicinal Chemistry, College of Pharmacy, 1 University Station, University of Texas, Austin, TX 78712, USADivision of Chemical Biology and Medicinal Chemistry, College of Pharmacy, 1 University Station, University of Texas, Austin, TX 78712, USA5-Halo-2-hydroxymuconates and 5-halo-2-hydroxy-2,4-pentadienoates are stable dienols that are proposed intermediates in bacterial meta-fission pathways for the degradation of halogenated aromatic compounds. The presence of the halogen raises questions about how the bulk and/or electronegativity of these substrates would affect enzyme catalysis or whether some pathway enzymes have evolved to accommodate it. To address these questions, 5-halo-2-hydroxymuconates and 5-halo-2-hydroxy-2,4-pentadienoates (5-halo = Cl, Br, F) were synthesized and a preliminary analysis of their enzymatic properties carried out. In aqueous buffer, 5-halo-2-hydroxy-2,4-pentadienoates rapidly equilibrate with the β,γ-unsaturated ketones. For the 5-chloro and 5-bromo derivatives, a slower conversion to the α,β-isomers follows. There is no detectable formation of the α,β-isomer for the 5-fluoro derivative. Kinetic parameters were also obtained for both sets of compounds in the presence of 4-oxalocrotonate tautomerase (4-OT) from Pseudomonas putida mt-2 and Leptothrix cholodnii SP-6. For 5-halo-2-hydroxymuconates, there are no major differences in the kinetic parameters for the two enzymes (following the formation of the β,γ-unsaturated ketones). In contrast, the L. cholodnii SP-6 4-OT is ≈10-fold less efficient than the P. putida mt-2 4-OT in the formation of the β,γ-unsaturated ketones and the α,β-isomers from the 5-halo-2-hydroxy-2,4-pentadienoates. The implications of these findings are discussed. The availability of these compounds will facilitate future studies of the haloaromatic catabolic pathways.https://doi.org/10.3762/bjoc.13.101dienolenzyme kineticsfluoridehalogen |
| spellingShingle | Tyler M. M. Stack William H. Johnson Jr. Christian P. Whitman Synthesis and enzymatic ketonization of the 5-(halo)-2-hydroxymuconates and 5-(halo)-2-hydroxy-2,4-pentadienoates Beilstein Journal of Organic Chemistry dienol enzyme kinetics fluoride halogen |
| title | Synthesis and enzymatic ketonization of the 5-(halo)-2-hydroxymuconates and 5-(halo)-2-hydroxy-2,4-pentadienoates |
| title_full | Synthesis and enzymatic ketonization of the 5-(halo)-2-hydroxymuconates and 5-(halo)-2-hydroxy-2,4-pentadienoates |
| title_fullStr | Synthesis and enzymatic ketonization of the 5-(halo)-2-hydroxymuconates and 5-(halo)-2-hydroxy-2,4-pentadienoates |
| title_full_unstemmed | Synthesis and enzymatic ketonization of the 5-(halo)-2-hydroxymuconates and 5-(halo)-2-hydroxy-2,4-pentadienoates |
| title_short | Synthesis and enzymatic ketonization of the 5-(halo)-2-hydroxymuconates and 5-(halo)-2-hydroxy-2,4-pentadienoates |
| title_sort | synthesis and enzymatic ketonization of the 5 halo 2 hydroxymuconates and 5 halo 2 hydroxy 2 4 pentadienoates |
| topic | dienol enzyme kinetics fluoride halogen |
| url | https://doi.org/10.3762/bjoc.13.101 |
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