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The biosynthetic pathway of the hallucinogen mescaline and its heterologous reconstruction

molecular Plant 2024年第7期17卷 1129-1150页

作者： Paula Berman Luis Alejandro de Haro Ana-Rita Cavaco Sayantan Panda Younghui Dong Nikolay Kuzmich Gabriel Lichtenstein Yoav Peleg Hila Harat Adam Jozwiaki Jianghua Cai Uwe Heinig sagit m.ir Ilana Rogachev Asaph Aharoni Department of Plant and Environmental Sciences Weizmann Institute of ScienceRehovot 7610001Israel Life Sciences Core Facilities Weizmann Institute of ScienceRehovot 7610001Israel The maurice and Vivienne Wohl Institute for Drug Discovery Weizmann Institute of ScienceRehovot 7610001Israel Present address:Department of Cell and metabolic Biology Leibniz Institute of Plant BiochemistryWeinberg 306120 Halle(Saale)Germany Department of molecular&Cellular Pharmacology University of Miami Miler School of MedicineMiamiFL 33136USA Department of Botany and Plant Sciences University of California RiversideRiversideCA 92521USA Laboratory of Plant Hormones and Development Regulation of Chongqing School of Life SciencesChongqing UniversityChongqing 401331China

mescaline,among the earliest identified natural hallucinogens,holds great potential in psychotherapy ***,despite the existence of a postulated biosynthetic pathway for more than half a century,the specific enzymes involved in this process are yet to be *** this study,we investigated the cactus Lophophora williamsii(Peyote),the largest known natural producer of the phenethylamine *** employed a multi-faceted approach,combining de novo whole-genome and transcriptome sequencing with comprehensive chemical profiling,enzymatic assays,molecular modeling,and pathway engineering for pathway *** identified four groups of enzymes responsible for the six catalytic steps in the mescaline biosynthetic pathway,and an N-methyltransferase enzyme that N-methylates all phenethylamine intermediates,likely modulating mescaline levels in ***,we reconstructed the mescaline biosynthetic pathway in both Nicotiana benthamiana plants and yeast cells,providing novel insights into several challenges hindering complete heterologous mescaline *** together,our study opens up avenues for exploration of sustainable production approaches and responsible utilization of mescaline,safeguarding this valuable natural resource for future generations.

关键词： mescaline Lophophora williamsi Peyote biosynthetic pathway de novo genome sequencing mo-lecular modeling

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Glycosylation of N-hydroxy-pipecolic acid equilibrates between systemic acquired resistance response and plant growth

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molecular Plant 2021年第3期14卷 440-455页

作者： Jianghua Cai Adam Jozwiak Lara Holoidovsky michael mmeijler sagit m.ir Ilana Rogachev Asaph Aharoni Department of Plant and Environmental Sciences Weizmann Institute of ScienceRehovot 761001Israel Department of Chemistry and the National Institute for Biotechnology in the Negev Ben-Gurion University of the NegevBe’er-Sheva 8410501Israel

N-hydroxy-pipecolic acid(NHP)activates plant systemic acquired resistance(SAR).Enhanced defense responses are typically accompanied by deficiency in plant development and *** of extensive studies on SAR induction,the effects of NHPmetabolismon plant growth remain largely *** this study,we discovered that NHP glycosylation is a critical factor that fine-tunes the tradeoff between SAR defense and plant *** demonstrated that a UDP-glycosyltransferase(UGT76B1)forming NHP glycoside(NHPG)controls the NHP to NHPG ***,the ugt76b1 mutant exhibits enhanced SAR response and an inhibitory effect on plant growth,while UGT76B1 overexpression attenuates SAR response,promotes growth,and delays senescence,indicating that NHP levels are dependent on UGT76B1 function in the course of ***,our results suggested that,upon pathogen attack,UGT76B1-mediated NHP glycosylation forms a‘‘hand brake’’on NHP accumulation by attenuating the positive regulation of NHP biosynthetic pathway genes,highlighting the complexity of SAR-associated *** addition,we showed that UGT76B1-mediated NHP glycosylation in the local site is important for fine-tuning SAR *** results implicate that engineering plant immunity through manipulating the NHP/NHPG ratio is a promising method to balance growth and defense response in crops.

关键词： N-hydroxy-pipecolic acid N-hydroxy-pipecolic acid glycoside UDP-glycosyltransferase glycosylation systemic acquired resistance plant growth

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