Sulfation of Phenolic Acids: Chemoenzymatic vs. Chemical Synthesis
Phenolic acids are known flavonoid metabolites, which typically undergo bioconjugation during phase II of biotransformation, forming sulfates, along with other conjugates. Sulfated derivatives of phenolic acids can be synthesized by two approaches: chemoenzymatically by 3′-phosphoadenosine-5′-phosph...
| Main Authors: | , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2022-12-01
|
| Series: | International Journal of Molecular Sciences |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1422-0067/23/23/15171 |
| _version_ | 1797463018232086528 |
|---|---|
| author | Viola Kolaříková Katerina Brodsky Lucie Petrásková Helena Pelantová Josef Cvačka Libor Havlíček Vladimír Křen Kateřina Valentová |
| author_facet | Viola Kolaříková Katerina Brodsky Lucie Petrásková Helena Pelantová Josef Cvačka Libor Havlíček Vladimír Křen Kateřina Valentová |
| author_sort | Viola Kolaříková |
| collection | DOAJ |
| description | Phenolic acids are known flavonoid metabolites, which typically undergo bioconjugation during phase II of biotransformation, forming sulfates, along with other conjugates. Sulfated derivatives of phenolic acids can be synthesized by two approaches: chemoenzymatically by 3′-phosphoadenosine-5′-phosphosulfate (PAPS)-dependent sulfotransferases or PAPS-independent aryl sulfotransferases such as those from <i>Desulfitobacterium hafniense</i>, or chemically using SO<sub>3</sub> complexes. Both approaches were tested with six selected phenolic acids (2-hydroxyphenylacetic acid (2-HPA), 3-hydroxyphenylacetic acid (3-HPA), 4-hydroxyphenylacetic acid (4-HPA), 3,4-dihydroxyphenylacetic acid (DHPA), 3-(4-hydroxyphenyl)propionic acid (4-HPP), and 3,4-dihydroxyphenylpropionic acid (DHPP)) to create a library of sulfated metabolites of phenolic acids. The sulfates of 3-HPA, 4-HPA, 4-HPP, DHPA, and DHPP were all obtained by the methods of chemical synthesis. In contrast, the enzymatic sulfation of monohydroxyphenolic acids failed probably due to enzyme inhibition, whereas the same reaction was successful for dihydroxyphenolic acids (DHPA and DHPP). Special attention was also paid to the counterions of the sulfates, a topic often poorly reported in synthetic works. The products obtained will serve as authentic analytical standards in metabolic studies and to determine their biological activity. |
| first_indexed | 2024-03-09T17:44:43Z |
| format | Article |
| id | doaj.art-9f6f3a2532b94d36af80c931e26bcdd0 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-09T17:44:43Z |
| publishDate | 2022-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-9f6f3a2532b94d36af80c931e26bcdd02023-11-24T11:14:26ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672022-12-0123231517110.3390/ijms232315171Sulfation of Phenolic Acids: Chemoenzymatic vs. Chemical SynthesisViola Kolaříková0Katerina Brodsky1Lucie Petrásková2Helena Pelantová3Josef Cvačka4Libor Havlíček5Vladimír Křen6Kateřina Valentová7Institute of Microbiology of the Czech Academy of Sciences, Vídeňská 1083, CZ 14220 Prague, Czech RepublicInstitute of Microbiology of the Czech Academy of Sciences, Vídeňská 1083, CZ 14220 Prague, Czech RepublicInstitute of Microbiology of the Czech Academy of Sciences, Vídeňská 1083, CZ 14220 Prague, Czech RepublicInstitute of Microbiology of the Czech Academy of Sciences, Vídeňská 1083, CZ 14220 Prague, Czech RepublicInstitute of Organic Chemistry and Biochemistry, Czech Academy of Sciences, Flemingovo nám. 2, CZ 16610 Prague, Czech RepublicInstitute of Experimental Botany of the Czech Academy of Sciences, Vídeňská 1083, CZ 14220 Prague, Czech RepublicInstitute of Microbiology of the Czech Academy of Sciences, Vídeňská 1083, CZ 14220 Prague, Czech RepublicInstitute of Microbiology of the Czech Academy of Sciences, Vídeňská 1083, CZ 14220 Prague, Czech RepublicPhenolic acids are known flavonoid metabolites, which typically undergo bioconjugation during phase II of biotransformation, forming sulfates, along with other conjugates. Sulfated derivatives of phenolic acids can be synthesized by two approaches: chemoenzymatically by 3′-phosphoadenosine-5′-phosphosulfate (PAPS)-dependent sulfotransferases or PAPS-independent aryl sulfotransferases such as those from <i>Desulfitobacterium hafniense</i>, or chemically using SO<sub>3</sub> complexes. Both approaches were tested with six selected phenolic acids (2-hydroxyphenylacetic acid (2-HPA), 3-hydroxyphenylacetic acid (3-HPA), 4-hydroxyphenylacetic acid (4-HPA), 3,4-dihydroxyphenylacetic acid (DHPA), 3-(4-hydroxyphenyl)propionic acid (4-HPP), and 3,4-dihydroxyphenylpropionic acid (DHPP)) to create a library of sulfated metabolites of phenolic acids. The sulfates of 3-HPA, 4-HPA, 4-HPP, DHPA, and DHPP were all obtained by the methods of chemical synthesis. In contrast, the enzymatic sulfation of monohydroxyphenolic acids failed probably due to enzyme inhibition, whereas the same reaction was successful for dihydroxyphenolic acids (DHPA and DHPP). Special attention was also paid to the counterions of the sulfates, a topic often poorly reported in synthetic works. The products obtained will serve as authentic analytical standards in metabolic studies and to determine their biological activity.https://www.mdpi.com/1422-0067/23/23/15171sulfationphenolic acidsaryl sulfotransferaseflavonoid metabolitesbiotransformation |
| spellingShingle | Viola Kolaříková Katerina Brodsky Lucie Petrásková Helena Pelantová Josef Cvačka Libor Havlíček Vladimír Křen Kateřina Valentová Sulfation of Phenolic Acids: Chemoenzymatic vs. Chemical Synthesis International Journal of Molecular Sciences sulfation phenolic acids aryl sulfotransferase flavonoid metabolites biotransformation |
| title | Sulfation of Phenolic Acids: Chemoenzymatic vs. Chemical Synthesis |
| title_full | Sulfation of Phenolic Acids: Chemoenzymatic vs. Chemical Synthesis |
| title_fullStr | Sulfation of Phenolic Acids: Chemoenzymatic vs. Chemical Synthesis |
| title_full_unstemmed | Sulfation of Phenolic Acids: Chemoenzymatic vs. Chemical Synthesis |
| title_short | Sulfation of Phenolic Acids: Chemoenzymatic vs. Chemical Synthesis |
| title_sort | sulfation of phenolic acids chemoenzymatic vs chemical synthesis |
| topic | sulfation phenolic acids aryl sulfotransferase flavonoid metabolites biotransformation |
| url | https://www.mdpi.com/1422-0067/23/23/15171 |
| work_keys_str_mv | AT violakolarikova sulfationofphenolicacidschemoenzymaticvschemicalsynthesis AT katerinabrodsky sulfationofphenolicacidschemoenzymaticvschemicalsynthesis AT luciepetraskova sulfationofphenolicacidschemoenzymaticvschemicalsynthesis AT helenapelantova sulfationofphenolicacidschemoenzymaticvschemicalsynthesis AT josefcvacka sulfationofphenolicacidschemoenzymaticvschemicalsynthesis AT liborhavlicek sulfationofphenolicacidschemoenzymaticvschemicalsynthesis AT vladimirkren sulfationofphenolicacidschemoenzymaticvschemicalsynthesis AT katerinavalentova sulfationofphenolicacidschemoenzymaticvschemicalsynthesis |