Biosynthesis of kratom opioids
© 2023 The Authors New Phytologist © 2023 New Phytologist Foundation.
| Veröffentlicht in: | The New phytologist. - 1979. - 240(2023), 2 vom: 05. Okt., Seite 757-769 |
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| 1. Verfasser: | |
| Weitere Verfasser: | , , , , , |
| Format: | Online-Aufsatz |
| Sprache: | English |
| Veröffentlicht: |
2023
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| Zugriff auf das übergeordnete Werk: | The New phytologist |
| Schlagworte: | Journal Article Research Support, Non-U.S. Gov't Mitragyna speciosa enol methyltransferase kratom mitragynine mitragynine microbial biosynthesis monoterpenoid indole alkaloid opioid synthetic biology mehr... |
| Zusammenfassung: | © 2023 The Authors New Phytologist © 2023 New Phytologist Foundation. Mitragynine, an analgesic alkaloid from the plant Mitragyna speciosa (kratom), offers a safer alternative to clinical opioids such as morphine, owing to its more favorable side effect profile. Although kratom has been traditionally used for stimulation and pain management in Southeast Asia, the mitragynine biosynthesis pathway has remained elusive. We embarked on a search for mitragynine biosynthetic genes from the transcriptomes of kratom and other members of the Rubiaceae family. We studied their functions in vitro and in vivo. Our investigations led to the identification of several reductases and an enol methyltransferase that forms a new clade within the SABATH methyltransferase family. Furthermore, we discovered a methyltransferase from Hamelia patens (firebush), which catalyzes the final step. With the tryptamine 4-hydroxylase from the psychedelic mushroom Psilocybe cubensis, we accomplished the four-step biosynthesis for mitragynine and its stereoisomer, speciogynine in both yeast and Escherichia coli when supplied with tryptamine and secologanin. Although we have yet to pinpoint the authentic hydroxylase and methyltransferase in kratom, our discovery completes the mitragynine biosynthesis. Through these breakthroughs, we achieved the microbial biosynthesis of kratom opioids for the first time. The remarkable enzyme promiscuity suggests the possibility of generating derivatives and analogs of kratom opioids in heterologous systems |
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| Beschreibung: | Date Completed 22.09.2023 Date Revised 24.09.2023 published: Print-Electronic Citation Status MEDLINE |
| ISSN: | 1469-8137 |
| DOI: | 10.1111/nph.19162 |