4-Hydroxyphenylacetate 3-Hydroxylase (4HPA3H): A Vigorous Monooxygenase for Versatile <i>O</i>-Hydroxylation Applications in the Biosynthesis of Phenolic Derivatives
4-Hydroxyphenylacetate 3-hydroxylase (4HPA3H) is a long-known class of two-component flavin-dependent monooxygenases from bacteria, including an oxygenase component (EC 1.14.14.9) and a reductase component (EC 1.5.1.36), with the latter being accountable for delivering the cofactor (reduced flavin)...
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MDPI AG
2024-01-01
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| Series: | International Journal of Molecular Sciences |
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| author | Ping Sun Shuping Xu Yuan Tian Pengcheng Chen Dan Wu Pu Zheng |
| author_facet | Ping Sun Shuping Xu Yuan Tian Pengcheng Chen Dan Wu Pu Zheng |
| author_sort | Ping Sun |
| collection | DOAJ |
| description | 4-Hydroxyphenylacetate 3-hydroxylase (4HPA3H) is a long-known class of two-component flavin-dependent monooxygenases from bacteria, including an oxygenase component (EC 1.14.14.9) and a reductase component (EC 1.5.1.36), with the latter being accountable for delivering the cofactor (reduced flavin) essential for <i>o</i>-hydroxylation. 4HPA3H has a broad substrate spectrum involved in key biological processes, including cellular catabolism, detoxification, and the biosynthesis of bioactive molecules. Additionally, it specifically hydroxylates the <i>o</i>-position of the C4 position of the benzene ring in phenolic compounds, generating high-value polyhydroxyphenols. As a non-P450 <i>o</i>-hydroxylase, 4HPA3H offers a viable alternative for the de novo synthesis of valuable natural products. The enzyme holds the potential to replace plant-derived P450s in the <i>o</i>-hydroxylation of plant polyphenols, addressing the current significant challenge in engineering specific microbial strains with P450s. This review summarizes the source distribution, structural properties, and mechanism of 4HPA3Hs and their application in the biosynthesis of natural products in recent years. The potential industrial applications and prospects of 4HPA3H biocatalysts are also presented. |
| first_indexed | 2024-03-08T09:52:51Z |
| format | Article |
| id | doaj.art-66544d60bff84dfc8bb6a163ac3b33a6 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-08T09:52:51Z |
| publishDate | 2024-01-01 |
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| spelling | doaj.art-66544d60bff84dfc8bb6a163ac3b33a62024-01-29T13:58:27ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672024-01-01252122210.3390/ijms250212224-Hydroxyphenylacetate 3-Hydroxylase (4HPA3H): A Vigorous Monooxygenase for Versatile <i>O</i>-Hydroxylation Applications in the Biosynthesis of Phenolic DerivativesPing Sun0Shuping Xu1Yuan Tian2Pengcheng Chen3Dan Wu4Pu Zheng5The Key Laboratory of Industrial Biotechnology, Ministry of Education, School of Biotechnology, Jiangnan University, Wuxi 214122, ChinaThe Key Laboratory of Industrial Biotechnology, Ministry of Education, School of Biotechnology, Jiangnan University, Wuxi 214122, ChinaThe Key Laboratory of Industrial Biotechnology, Ministry of Education, School of Biotechnology, Jiangnan University, Wuxi 214122, ChinaThe Key Laboratory of Industrial Biotechnology, Ministry of Education, School of Biotechnology, Jiangnan University, Wuxi 214122, ChinaThe Key Laboratory of Industrial Biotechnology, Ministry of Education, School of Biotechnology, Jiangnan University, Wuxi 214122, ChinaThe Key Laboratory of Industrial Biotechnology, Ministry of Education, School of Biotechnology, Jiangnan University, Wuxi 214122, China4-Hydroxyphenylacetate 3-hydroxylase (4HPA3H) is a long-known class of two-component flavin-dependent monooxygenases from bacteria, including an oxygenase component (EC 1.14.14.9) and a reductase component (EC 1.5.1.36), with the latter being accountable for delivering the cofactor (reduced flavin) essential for <i>o</i>-hydroxylation. 4HPA3H has a broad substrate spectrum involved in key biological processes, including cellular catabolism, detoxification, and the biosynthesis of bioactive molecules. Additionally, it specifically hydroxylates the <i>o</i>-position of the C4 position of the benzene ring in phenolic compounds, generating high-value polyhydroxyphenols. As a non-P450 <i>o</i>-hydroxylase, 4HPA3H offers a viable alternative for the de novo synthesis of valuable natural products. The enzyme holds the potential to replace plant-derived P450s in the <i>o</i>-hydroxylation of plant polyphenols, addressing the current significant challenge in engineering specific microbial strains with P450s. This review summarizes the source distribution, structural properties, and mechanism of 4HPA3Hs and their application in the biosynthesis of natural products in recent years. The potential industrial applications and prospects of 4HPA3H biocatalysts are also presented.https://www.mdpi.com/1422-0067/25/2/12224-hydroxyphenylacetate 3-hydroxylase (4HPA3H)two-component flavin-dependent monooxygenase<i>o</i>-hydroxylationplant polyhydroxyphenolsplant-derived P450-alternative monooxygenases |
| spellingShingle | Ping Sun Shuping Xu Yuan Tian Pengcheng Chen Dan Wu Pu Zheng 4-Hydroxyphenylacetate 3-Hydroxylase (4HPA3H): A Vigorous Monooxygenase for Versatile <i>O</i>-Hydroxylation Applications in the Biosynthesis of Phenolic Derivatives International Journal of Molecular Sciences 4-hydroxyphenylacetate 3-hydroxylase (4HPA3H) two-component flavin-dependent monooxygenase <i>o</i>-hydroxylation plant polyhydroxyphenols plant-derived P450-alternative monooxygenases |
| title | 4-Hydroxyphenylacetate 3-Hydroxylase (4HPA3H): A Vigorous Monooxygenase for Versatile <i>O</i>-Hydroxylation Applications in the Biosynthesis of Phenolic Derivatives |
| title_full | 4-Hydroxyphenylacetate 3-Hydroxylase (4HPA3H): A Vigorous Monooxygenase for Versatile <i>O</i>-Hydroxylation Applications in the Biosynthesis of Phenolic Derivatives |
| title_fullStr | 4-Hydroxyphenylacetate 3-Hydroxylase (4HPA3H): A Vigorous Monooxygenase for Versatile <i>O</i>-Hydroxylation Applications in the Biosynthesis of Phenolic Derivatives |
| title_full_unstemmed | 4-Hydroxyphenylacetate 3-Hydroxylase (4HPA3H): A Vigorous Monooxygenase for Versatile <i>O</i>-Hydroxylation Applications in the Biosynthesis of Phenolic Derivatives |
| title_short | 4-Hydroxyphenylacetate 3-Hydroxylase (4HPA3H): A Vigorous Monooxygenase for Versatile <i>O</i>-Hydroxylation Applications in the Biosynthesis of Phenolic Derivatives |
| title_sort | 4 hydroxyphenylacetate 3 hydroxylase 4hpa3h a vigorous monooxygenase for versatile i o i hydroxylation applications in the biosynthesis of phenolic derivatives |
| topic | 4-hydroxyphenylacetate 3-hydroxylase (4HPA3H) two-component flavin-dependent monooxygenase <i>o</i>-hydroxylation plant polyhydroxyphenols plant-derived P450-alternative monooxygenases |
| url | https://www.mdpi.com/1422-0067/25/2/1222 |
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