Biosynthesis of kratom opioids
New Phytologist July 30, 2023 Kyunghee Kim, Mohammadamin Shahsavarani, Jorge Jonathan Oswaldo Garza-García et al. 43 citations
Mitragynine, an analgesic alkaloid from the kratom plant, has a more favorable side effect profile than clinical opioids like morphine. The biosynthetic pathway for mitragynine was previously unknown. Researchers identified several reductases and an enol methyltransferase forming a new clade within the SABATH methyltransferase family from kratom and related Rubiaceae transcriptomes. They also discovered a methyltransferase from Hamelia patens that catalyzes the final step. Using a tryptamine 4-hydroxylase from Psilocybe cubensis, they achieved four-step biosynthesis of mitragynine and its stereoisomer speciogynine in yeast and E. coli supplied with tryptamine and secologanin. This marks the first microbial biosynthesis of kratom opioids. The enzyme promiscuity suggests potential for generating derivatives and analogs.