GNPSapplication/xmlftp://massive.ucsd.edu/v02/MSV000083272/primaryOK200MetabolomicsMultiomicsJing-Ke WengQ ExactiveArabidopsis Thaliana (ncbitaxon:3702)https://massive.ucsd.edu/ProteoSAFe/dataset.jsp?task=d167ae682be843d8a6a6de8bf74df9e5wengj@wi.mit.eduWhitehead Institute for Biomedical ResearchGNPS23MS:1002864 - No post-translational-modifications are included in the identified peptides of this datasetKava (Piper methysticum) is an ethnomedicinal shrub native to the Polynesian islands with well-established anxiolytic and analgesic properties. Its main psychoactive principles, kavalactones, form a unique class of polyketides that interact with the human central nervous system through mechanisms distinct from those of conventional psychiatric drugs. However, an unknown biosynthetic machinery and difficulty in chemical synthesis hinder the therapeutic use of kavalactones. In addition, kava also produces flavokavains, which are chalconoids with anticancer properties structurally related to kavalactones. Here, we report de novo elucidation of the key enzymes of the kavalactone and flavokavain biosynthetic network. We present the structural basis for the evolutionary development of a pair of paralogous styrylpyrone synthases that establish the kavalactone scaffold and the catalytic mechanism of a regio- and stereo-specific kavalactone reductase that produces a subset of chiral kavalactones. We further demonstrate the feasibility of engineering styrylpyrone production in heterologous hosts, thus opening a way to develop kavalactone-based non-addictive psychiatric therapeutics through synthetic biology.The biosynthetic origin of psychoactive kavalactones in kava.Pluskal Tomáš T, Torrens-Spence Michael P MP, Fallon Timothy R TR, De Abreu Andrea A, Shi Cindy H CH, Weng Jing-Ke JKForms, distinct from, Therapy, Kava, methysticums, human being, neuraxis, foramen, single-organism developmental process, Central, Biocatalysts, Cerebrospinal Axis, Biologies, Piper methysticums, enzyme activity, Kawa Kawas, foramina, Central Nervous Systems, dIKK-gamma, Cerebrospinal, Central Nervous, development, Ketides, IKKgamma, DmIKKgamma, Nervous Systems, Kava Kava, dIKK, DmIKK-gamma, Systems, cerebrospinal axis, Kenny, Polyketide, kava, dmIKKgamma, IKK[[gamma]], Kavas, IKKg, KEY, Key, Synthetic, Nervous System, ostium, systema nervosum centrale, CNS, enzymes, Biology, Dmikkgamma, Engineerings, Kava Kavas, Synthetic., IKK-gamma, present in organism, CG16910, man, Treatments, human, Axis, Kawa, drugs, Enzyme, DmelCG16910, IKK, Therapeutic, Cerebrospinal Axi, medicine, Piper methysticum, opening, Biocatalyst, Kawa Kawa, Therapies, Synthetic Biologies, Axi, Treatment, ostia, Piper, Kawascoxa vara, Kava, flavanone synthase activity, methysticums, sucrose 6-phosphate synthase activity, malonyl-CoA:4-coumaroyl-CoA malonyltransferase (cyclizing), selD/sps1, SRML1, Chédiak-Higashi syndrome, Arbisopsis thaliana, Chediak Higashi syndrome, ischiocoxopodopatellar syndrome with or without pulmonary arterial hypertension, ischiopatellar dysplasia, CHS, l(2)SH2 1599, PAPT, Piper methysticums, ChC)diak-Higashi disease, Kawa Kawas, dSPS1, SPS, SPDSY, SUPERSHOOT 1, DOCS, selD, anon-WO0172774.145, SeS, ptuf, ischiocoxopodopatellar syndrome, UDPglucose-fructose-phosphate glucosyltransferase activity, anon-WO0172774.146, Dm-SelD, dsps1, F3O9_21, AW111620, Kava Kava, UDP-glucose:D-fructose-6-phosphate 2-alpha-D-glucosyltransferase activity, small patella syndrome, congenital coxa vara, sucrose phosphate synthetase activity, flavonone synthase activity, Arabidopsis thaliana (thale cress), kava, Coxo-podo-patellar syndrome, chalcone synthase activity, Chédiak-Higashi disease, F3O9.21, l(2)k12303, ptf1, DmelCG8553, uridine diphosphoglucose-fructose phosphate glucosyltransferase activity, Kavas, tarsal synostosis, AI505014, thale cress, SPMSY, mouse-ear cress, chalcone synthetase activity, patella aplasia, ChC)diak-Higashi-Steinbrink syndrome, 142926_at, Chédiak-Higashi-Steinbrink syndrome, sucrosephosphate-UDP glucosyltransferase activity, Ysg3, BUS1, UDP-glucose-fructose-phosphate glucosyltransferase activity, Kava Kavas, SRS, coxopodopatellar syndrome, BUSHY 1, ptuf1, ICPPS, MRSR, Kawa, thale-cress, UDPglucose:D-fructose-6-phosphate 2-alpha-D-glucosyltransferase activity, CG8553, Chediak - Steinbrinck anomaly, Piper methysticum, SELD, Kawa Kawa, cytochrome p450 79f1, Arabis thaliana., Dm SelD, Chediak-Higashi syndrome, patella aplasia and tarsal synostosis, SpS, l(2)SH1599, Sps2, Piper, Kawas, SPS1, Scott-Taor syndrome, AA589574, 1110046B24Rik, sucrose phosphate-uridine diphosphate glucosyltransferase activityKava, Kawa, Kava., methysticums, Kava Kava, Piper methysticum, Kava Kavas, Kawa Kawa, Piper methysticums, kava, Kawa Kawas, Piper, Kavas, Kawassucrose 6-phosphate synthase activity, SRML1, Chédiak-Higashi syndrome, ischiopatellar dysplasia, Piper methysticums, ChC)diak-Higashi disease, Kawa Kawas, dSPS1, DOCS, Arabis thaliana, selD, SeS, ischiocoxopodopatellar syndrome, UDPglucose-fructose-phosphate glucosyltransferase activity, Dm-SelD, dsps1, F3O9_21, AW111620, Kava Kava, UDP-glucose:D-fructose-6-phosphate 2-alpha-D-glucosyltransferase activity, small patella syndrome, congenital coxa vara, sucrose phosphate synthetase activity, Coxo-podo-patellar syndrome, F3O9.21, DmelCG8553, tarsal synostosis, AI505014, SPMSY, chalcone synthetase activity, patella aplasia, 142926_at, sucrosephosphate-UDP glucosyltransferase activity, Ysg3, UDP-glucose-fructose-phosphate glucosyltransferase activity, coxopodopatellar syndrome, BUSHY 1, ptuf1, thale-cress, UDPglucose:D-fructose-6-phosphate 2-alpha-D-glucosyltransferase activity, SELD, cytochrome p450 79f1, Dm SelD, SpS, l(2)SH1599, Sps2, SPS1, Scott-Taor syndrome, AA589574, 1110046B24Rik, sucrose phosphate-uridine diphosphate glucosyltransferase activity, coxa vara, Kava, flavanone synthase activity, methysticums, malonyl-CoA:4-coumaroyl-CoA malonyltransferase (cyclizing), selD/sps1, Arbisopsis thaliana, Chediak Higashi syndrome, ischiocoxopodopatellar syndrome with or without pulmonary arterial hypertension, CHS, l(2)SH2 1599, PAPT, introduction., SPS, SPDSY, SUPERSHOOT 1, anon-WO0172774.145, ptuf, anon-WO0172774.146, flavonone synthase activity, Arabidopsis thaliana (thale cress), kava, chalcone synthase activity, Chédiak-Higashi disease, background, l(2)k12303, ptf1, uridine diphosphoglucose-fructose phosphate glucosyltransferase activity, Kavas, thale cress, mouse-ear cress, ChC)diak-Higashi-Steinbrink syndrome, Chédiak-Higashi-Steinbrink syndrome, BUS1, Kava Kavas, SRS, ICPPS, MRSR, Kawa, CG8553, Chediak - Steinbrinck anomaly, Piper methysticum, Kawa Kawa, Chediak-Higashi syndrome, patella aplasia and tarsal synostosis, Piper, KawasfalseGNPS - Expression of kava SPS1, SPS2, and CHS in Arabidopsis thalianaExpression of kava SPS1, SPS2, and CHS in Arabidopsis thaliana tt4-2 background.Fri Dec 21 06:56:00 GMT 2018MSV00008327231332312