{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,12]],"date-time":"2026-09-12T20:01:44Z","timestamp":1789243304299,"version":"build-2803163510"},"reference-count":30,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2023,7,30]],"date-time":"2023-07-30T00:00:00Z","timestamp":1690675200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000038","name":"Natural Sciences and Engineering Research Council of Canada","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000038","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000240","name":"New Brunswick Innovation Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000240","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["nph.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["New Phytologist"],"published-print":{"date-parts":[[2023,10]]},"abstract":"Summary<\/jats:title>\n \n \n \n \n Mitragynine, an analgesic alkaloid from the plant\n Mitragyna speciosa<\/jats:italic>\n (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.\n <\/jats:p>\n <\/jats:list-item>\n \n \n 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\n in\u00a0vitro<\/jats:italic>\n and\n in\u00a0vivo<\/jats:italic>\n .\n <\/jats:p>\n <\/jats:list-item>\n \n \n 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\n Hamelia patens<\/jats:italic>\n (firebush), which catalyzes the final step. With the tryptamine 4\u2010hydroxylase from the psychedelic mushroom\n Psilocybe cubensis<\/jats:italic>\n , we accomplished the four\u2010step biosynthesis for mitragynine and its stereoisomer, speciogynine in both yeast and\n Escherichia coli<\/jats:italic>\n when supplied with tryptamine and secologanin.\n <\/jats:p>\n <\/jats:list-item>\n \n 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.<\/jats:p>\n <\/jats:list-item>\n <\/jats:list>\n <\/jats:p>","DOI":"10.1111\/nph.19162","type":"journal-article","created":{"date-parts":[[2023,7,31]],"date-time":"2023-07-31T00:45:38Z","timestamp":1690764338000},"page":"757-769","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":46,"title":["Biosynthesis of kratom opioids"],"prefix":"10.1111","volume":"240","author":[{"given":"Kyunghee","family":"Kim","sequence":"first","affiliation":[{"name":"Department of Biological Sciences Brock University St. Catharines ON L2S 3A1 Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7011-2775","authenticated-orcid":false,"given":"Mohammadamin","family":"Shahsavarani","sequence":"additional","affiliation":[{"name":"Department of Chemistry University of New Brunswick Fredericton NB E3B 5A3 Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jorge Jonathan Oswaldo","family":"Garza\u2010Garc\u00eda","sequence":"additional","affiliation":[{"name":"Department of Chemistry University of New Brunswick Fredericton NB E3B 5A3 Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jack Edward","family":"Carlisle","sequence":"additional","affiliation":[{"name":"Department of Chemistry University of New Brunswick Fredericton NB E3B 5A3 Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Guo","sequence":"additional","affiliation":[{"name":"Department of Chemistry University of New Brunswick Fredericton NB E3B 5A3 Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8925-9382","authenticated-orcid":false,"given":"Vincenzo","family":"De Luca","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences Brock 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synthase controls flux in the formation of monoterpenoid indole alkaloids in a Catharanthus roseus mutant","volume":"25","author":"Qu Y","year":"2017","journal-title":"Planta"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1021\/jacs.2c13644"},{"key":"e_1_2_9_24_1","doi-asserted-by":"crossref","DOI":"10.1016\/j.mec.2022.e00215","article-title":"Improved protein glycosylation enabled heterologous biosynthesis of monoterpenoid indole alkaloids and their unnatural derivatives in yeast","volume":"16","author":"Shahsavarani M","year":"2022","journal-title":"Metabolic Engineering 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