Dr. Duke’s Phytochemical and Ethnobotanical Database [12] is a free factual database hosted by the Agricultural Research Service (ARS) at the U.S. Department of Agriculture (USDA). The latest update of the database was 1996. The search term ‘oryza sativa’ was used. SetupX [13] is a study design database for metabolomic projects. It currently contains raw data and assigned meta-data from GCTOF mass spectrometry metabolic profiling experiments that were annotated by the BinBase mass spectral database [14]. Currently 40 species are covered and more than 14,000 public and non-public experimental datasets are available. The search term ‘oryza sativa’ was used. The RiceCyc database [15] is developed and curated by Gramene (Resource for Comparative Grass Genomics) [16]. RiceCyc is a catalog of known and predicted biochemical pathways from rice (oryza sativa). The database (version 2.0.2; oryza sativa japonica; strain: nipponbare) was fully downloaded and data was analyzed as text. The KEGG database [17] is an important pathway and metabolic network database covering a wide range of organisms. The database was queried with the available online tools and content was downloaded in raw format and processed for species ‘oryza sativa’, coded as osa and eosa string. The KNApSAcK database [18] is a species-metabolite relationship database containing 23,287 metabolite entries and 46,093 metabolite-species pair entries (version 1.200.02). It was searched via the web frontend [19]. Mostly secondary plant metabolites are covered. The Reactome database [20] (version 26) was queried using ‘oryza sativa’ as search term. Reactome contains curated human pathways and additional 22 non-human species with parts of the data obtained by orthology mapping approaches for genes and proteins in case whole-genome sequence data was available. For patent searches the CAS database [7], the IBM Chemical Search alpha [21] and IBM Chemical Patent search beta and the SureChem patent database [22] were used. The CAS DB and SureChem DB allowed factual searches with the keywords ‘oryza sativa’ or ‘rice’ and also Markush structure search [23] which is specifically used for patent searches. Surechem allows subscription based download of structures found in patents. In our case the Compound DBs Ortholog/Pathway DBs Patent DBs PubChem/PubMed CAS Beilstein SetupX Dr. Duke DNP KNApSAcK DB KEGG RiceCyc Reactome IBM Patent Search .3000 .1400 554 268 201 55 48 3661 1500 396 9780 The table reports all organic metabolites with possible organism mix-ups including bacterial and fungal metabolites or pesticides and drugs. Search date October 2008. doi:10.1371/journal.pone.0005440.t001 PLoS ONE | www.plosone.org 3 May 2009 | Volume 4 | Issue 5 | e5440 Data Exchange in Chemistry IBM patent database was used to export all detected chemical structures from all world patents (WIPO). Results We here report the results for each database query and discuss search capabilities and problems (Table 1). Mostly organic molecules are reported, leaving out the majority of metals and other rare earth elements. Data on metals and trace metals can be relatively easily acquired with inductively coupled plasma mass spectrometry (ICP-MS) which is not the case for small organic molecules. Molecules larger than 2000 Dalton and special compound classes like glycans and peptides are also excluded. The analysis of those substance classes are covered by glycomics and proteomics based techniques. All retrieved results with 112,000 factual data points on rice metabolites reported here can be downloaded from the supplement section at the authors’ homepage [24]. Dictionary of Natural Products The commercially available Dictionary of Natural Products was used over its online web frontend [8]. The web frontend allows structure and substructure searches as well as text searches. The DNP database itself covers most of the natural product publications and small molecules and peptide structures from animals, plants and fungi. DNP is the largest curated database of natural products covering more than 200,000 entries. Taxo- nomic names and physicochemical properties and secondary literature are included for most of the structures. No connections or links to other life sciences databases exists. One major caveat is that chemical structures cannot be downloaded in bulk but only one-by-one. Moreover, structures are only shown as graphics and not as chemical structure files which would be necessary to computationally analyze and compare compounds. However, only 55 metabolites were retrieved when querying DNP for metabolites in rice using the DNP taxonomy search. This number is certainly too low as, for example, many proteinogenic amino acids and other primary metabolites are not included in DNP which focuses on secondary metabolism. Common metabolites like arginine are covered in DNP and can be found in rice, but no taxonomy information is assigned. The mixed mixed mixed clean clean clean clean mixed mixed mixed mixed contains pesticides and drugs contains pesticides and drugs contains pesticides and drugs with relative concentrations with relative concentrations few mixed with multi species few other species included putative compounds included putative compounds included putative compounds included contains pesticides and drugs Table 1. Number of small molecules found in oryza sativa by database search. Database Oryzae compounds Mix-up Comment