Proteomic analysis of Artemisia annua – towards elucidating the biosynthetic pathways of the antimalarial pro-drug artemisinin

BMC Plant Biology

Research Article

Geoffrey D. Brown¹  Brian Flatley¹  Chhaya Patole¹  Laura Bryant¹  Rainer Cramer¹ 

[1] Department of Chemistry, Whiteknights, RG6 6AD, Reading, United Kingdom;

关键词: Artemisia annua;    Artemisinin;    Malaria;    Mass spectrometry;    Plant proteomics;    Proteogenomics;    Trichomes;   

DOI  :  10.1186/s12870-015-0565-7

 received in 2015-01-09, accepted in 2015-07-01,  发布年份 2015

来源: Springer

【 摘 要 】

BackgroundMS-based proteomics was applied to the analysis of the medicinal plant Artemisia annua, exploiting a recently published contig sequence database (Graham et al. (2010) Science 327, 328–331) and other genomic and proteomic sequence databases for comparison. A. annua is the predominant natural source of artemisinin, the precursor for artemisinin-based combination therapies (ACTs), which are the WHO-recommended treatment for P. falciparum malaria.ResultsThe comparison of various databases containing A. annua sequences (NCBInr/viridiplantae, UniProt/viridiplantae, UniProt/A. annua, an A. annua trichome Trinity contig database, the above contig database and another A. annua EST database) revealed significant differences in respect of their suitability for proteomic analysis, showing that an organism-specific database that has undergone extensive curation, leading to longer contig sequences, can greatly increase the number of true positive protein identifications, while reducing the number of false positives. Compared to previously published data an order-of-magnitude more proteins have been identified from trichome-enriched A. annua samples, including proteins which are known to be involved in the biosynthesis of artemisinin, as well as other highly abundant proteins, which suggest additional enzymatic processes occurring within the trichomes that are important for the biosynthesis of artemisinin.ConclusionsThe newly gained information allows for the possibility of an enzymatic pathway, utilizing peroxidases, for the less well understood final stages of artemisinin’s biosynthesis, as an alternative to the known non-enzymatic in vitro conversion of dihydroartemisinic acid to artemisinin. Data are available via ProteomeXchange with identifier PXD000703.

【 授权许可】

Unknown   
© Bryant et al. 2015. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.