Dataset Information

GNPS Kava enzyme expression in Nicotiana benthamiana

ABSTRACT: The key enzymes of the kavalactone biosynthetic pathway from Piper methysticum were heterologuously expressed using agrobacterium infiltration in Nicotiana benthamiana. In addition, an isotopically labeled substrate, cinnamic acid-d6, was injected into the Nicotiana plants. Related to this study: Pluskal, T., Torrens-Spence, M.P., Fallon, T.R. et al. The biosynthetic origin of psychoactive kavalactones in kava. Nat. Plants 5, 867 (2019). https://doi.org/10.1038/s41477-019-0474-0

OTHER RELATED OMICS DATASETS IN: MSV000083277MSV000083276

INSTRUMENT(S): Q Exactive

ORGANISM(S): Nicotiana Benthamiana (ncbitaxon:4100)

SUBMITTER: Jing-Ke Weng

PROVIDER: MSV000087906 | GNPS | Thu Jul 29 04:34:00 BST 2021

REPOSITORIES: GNPS

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Publications

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 JK

Nature plants 20190722 8

Kava (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 ...[more]

PMID: 31332312

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Project description:A highly recurrent, somatic L265P mutation in the TIR domain of the signaling adapter MYD88 constitutively activates NF-kB. It occurs in nearly all human patients with Waldenström’s macroglobulinemia (WM), a B cell malignancy caused by IgM-expressing cells. Here we introduced an inducible leucine to proline point mutation into the mouse Myd88 locus, at the orthologous position L252P. When the mutation was introduced early during B cell development, B cells developed normally. However, IgM-expressing plasma cells accumulated with age in spleen and bone, leading to more than 20-fold elevated serum IgM titers. When introduced into germinal center B cells in the context of an immunization, the Myd88L252P mutation caused prolonged persistence of antigen-specific serum IgM and elevated numbers of antigen-specific IgM plasma cells. Myd88L252P-expressing B cells switched normally, but plasma cells expressing other immunoglobulin isotypes did not increase in numbers, implying that IgM expression may be required for the observed cellular expansion. In order to test whether the Myd88L252P mutation can cause clonal expansions, we introduced it into a small fraction of CD19-positive B cells. In this scenario, five out of five mice developed monoclonal IgM serum paraproteins accompanied by an expansion of clonally related plasma cells that expressed mostly hypermutated VDJ regions. Taken together, our data suggest that the Myd88L252P mutation is sufficient to promote aberrant survival and expansion of IgM-expressing plasma cells which in turn can cause IgM monoclonal gammopathy of undetermined significance (MGUS), the premalignant condition that precedes WM. References: 1. Shevchenko A, Tomas H, Havli J, Olsen JV, Mann M. In-gel digestion for mass spectrometric characterization of proteins and proteomes. Nat Protoc (2006) 1:2856–2860. doi:10.1038/nprot.2006.468, 2. Rappsilber J, Mann M, Ishihama Y. Protocol for micro-purification, enrichment, pre-fractionation and storage of peptides for proteomics using StageTips. Nat Protoc (2007) 2:1896–1906. doi:10.1038/nprot.2007.261, 3. Cox J, Neuhauser N, Michalski A, Scheltema RA, Olsen JV, Mann M. Andromeda: A Peptide Search Engine Integrated into the MaxQuant Environment. J Proteome Res (2011) 10:1794–1805. doi:10.1021/pr101065j, 4. Cox J, Mann M. MaxQuant enables high peptide identification rates, individualized p.p.b.-range mass accuracies and proteome-wide protein quantification. Nat Biotechnol (2008) 26:1367–1372. doi:10.1038/nbt.1511.

Dataset Information

GNPS Kava enzyme expression in Nicotiana benthamiana

Publications

The biosynthetic origin of psychoactive kavalactones in kava.

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