New insights into substrate preference and aryl ring migration mechanism for isoflavonoid biosynthesis
Isoflavonoids are an essential source of bioactive compounds. Due to their enormous potential for human health, the demand for isoflavonoids is rising. Isoflavonoid synthase (IFS), a unique P450 monooxygenase, catalyzes the rate-limiting step in the biosynthesis of isoflavonoids. Here, IFS enzymes f...
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| Format: | Article |
| Language: | English |
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Elsevier
2023-01-01
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| Series: | Current Research in Biotechnology |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2590262823000242 |
| _version_ | 1827590173332865024 |
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| author | Moon Sajid Parwinder Kaur |
| author_facet | Moon Sajid Parwinder Kaur |
| author_sort | Moon Sajid |
| collection | DOAJ |
| description | Isoflavonoids are an essential source of bioactive compounds. Due to their enormous potential for human health, the demand for isoflavonoids is rising. Isoflavonoid synthase (IFS), a unique P450 monooxygenase, catalyzes the rate-limiting step in the biosynthesis of isoflavonoids. Here, IFS enzymes from five different plants are characterized for isoflavonoid biosynthesis in yeast. Although IFS generally prefers liquiritigenin as a substrate, this is the first time an IFS from Pueraria candollei has been characterised with a preference for naringenin. Co-expression of 2-hydroxyisoflavonoid dehydratase (HID) with IFS significantly improves isoflavonoids biosynthesis. However, a preference of IFS towards particular HID enzymes types was observed in this study. Additionally, the protein conformational basis of aryl ring migration mechanism has been explored for Onobrychis viciifolia IFS, P. candollei IFS, and CYP82D26 and compared with other P450 enzymes that accept the same substrates but do not produce isoflavonoids. Protein structure and docking analysis based on key amino acids, heme orientation, and IFS promiscuity has led us to suggest a new mechanism for aryl ring migration. Characterisation of IFS for efficiency, substrate preference, and understanding of aryl ring migration mechanism will help advance heterologous biosynthesis and protein engineering efforts. |
| first_indexed | 2024-03-09T01:12:08Z |
| format | Article |
| id | doaj.art-e36ff4d58a0546d6abf75b1b87fd93b2 |
| institution | Directory Open Access Journal |
| issn | 2590-2628 |
| language | English |
| last_indexed | 2024-03-09T01:12:08Z |
| publishDate | 2023-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Current Research in Biotechnology |
| spelling | doaj.art-e36ff4d58a0546d6abf75b1b87fd93b22023-12-11T04:16:52ZengElsevierCurrent Research in Biotechnology2590-26282023-01-016100142New insights into substrate preference and aryl ring migration mechanism for isoflavonoid biosynthesisMoon Sajid0Parwinder Kaur1UWA School of Agriculture and Environment, The University of Western Australia, Perth, WA 6009, AustraliaCorresponding author.; UWA School of Agriculture and Environment, The University of Western Australia, Perth, WA 6009, AustraliaIsoflavonoids are an essential source of bioactive compounds. Due to their enormous potential for human health, the demand for isoflavonoids is rising. Isoflavonoid synthase (IFS), a unique P450 monooxygenase, catalyzes the rate-limiting step in the biosynthesis of isoflavonoids. Here, IFS enzymes from five different plants are characterized for isoflavonoid biosynthesis in yeast. Although IFS generally prefers liquiritigenin as a substrate, this is the first time an IFS from Pueraria candollei has been characterised with a preference for naringenin. Co-expression of 2-hydroxyisoflavonoid dehydratase (HID) with IFS significantly improves isoflavonoids biosynthesis. However, a preference of IFS towards particular HID enzymes types was observed in this study. Additionally, the protein conformational basis of aryl ring migration mechanism has been explored for Onobrychis viciifolia IFS, P. candollei IFS, and CYP82D26 and compared with other P450 enzymes that accept the same substrates but do not produce isoflavonoids. Protein structure and docking analysis based on key amino acids, heme orientation, and IFS promiscuity has led us to suggest a new mechanism for aryl ring migration. Characterisation of IFS for efficiency, substrate preference, and understanding of aryl ring migration mechanism will help advance heterologous biosynthesis and protein engineering efforts.http://www.sciencedirect.com/science/article/pii/S2590262823000242IsoflavonoidsIsoflavonoid synthase (IFS)Aryl ring migration mechanismHeterologous biosynthesis |
| spellingShingle | Moon Sajid Parwinder Kaur New insights into substrate preference and aryl ring migration mechanism for isoflavonoid biosynthesis Current Research in Biotechnology Isoflavonoids Isoflavonoid synthase (IFS) Aryl ring migration mechanism Heterologous biosynthesis |
| title | New insights into substrate preference and aryl ring migration mechanism for isoflavonoid biosynthesis |
| title_full | New insights into substrate preference and aryl ring migration mechanism for isoflavonoid biosynthesis |
| title_fullStr | New insights into substrate preference and aryl ring migration mechanism for isoflavonoid biosynthesis |
| title_full_unstemmed | New insights into substrate preference and aryl ring migration mechanism for isoflavonoid biosynthesis |
| title_short | New insights into substrate preference and aryl ring migration mechanism for isoflavonoid biosynthesis |
| title_sort | new insights into substrate preference and aryl ring migration mechanism for isoflavonoid biosynthesis |
| topic | Isoflavonoids Isoflavonoid synthase (IFS) Aryl ring migration mechanism Heterologous biosynthesis |
| url | http://www.sciencedirect.com/science/article/pii/S2590262823000242 |
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