TY  - JOUR
PY  - 2023//
TI  - Biosynthesis of kratom opioids
JO  - New phytologist, The
A1  - Kim, Kyunghee
A1  - Shahsavarani, Mohammadamin
A1  - Garza-García, Jorge Jonathan Oswaldo
A1  - Carlisle, Jack Edward
A1  - Guo, Jun
A1  - De Luca, Vincenzo
A1  - Qu, Yang
SP  - ePub
EP  - ePub
VL  - ePub
IS  - ePub
N2  - 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.<p />  <p>Language: en</p>
LA  - en
SN  - 0028-646X
UR  - http://dx.doi.org/10.1111/nph.19162
ID  - ref1
ER  -