The TriForC database: a comprehensive up-to-date resource of plant triterpene biosynthesis

Abstract

Triterpenes constitute a large and important class of plant natural products with diverse structures and functions. Their biological roles range from membrane structural components over plant hormones to specialized plant defence compounds. Furthermore, triterpenes have great potential for a variety of commercial applications such as vaccine adjuvants, anti-cancer drugs, food supplements and agronomic agents. Their biosynthesis is carried out through complicated, branched pathways by multiple enzyme types that include oxidosqualene cyclases, cytochrome P450s, and UDP-glycosyltransferases. Given that the number of characterized triterpene biosynthesis enzymes has been growing fast recently, the need for a database specifically focusing on triterpene enzymology became eminent. Here, we present the TriForC database (http://bioinformatics.psb.ugent.be/triforc/), encompassing a comprehensive catalogue of triterpene biosynthesis enzymes. This highly interlinked database serves as a user-friendly access point to versatile data sets of enzyme and compound features, enabling the scanning of a complete catalogue of experimentally validated triterpene enzymes, their substrates and products, as well as the pathways they constitute in various plant species. The database can be accessed by direct browsing or through convenient search tools including keyword, BLAST, plant species and substructure options. This database will facilitate gene mining and creating genetic toolboxes for triterpene synthetic biology.

Figure 1.

Overview of plant triterpene biosynthesis. Plants produce diverse types of triterpenes, some of which are depicted here. BAS, β-amyrin synthase; BOS, baccharis oxide synthase; CAS, cycloartenol synthase; CPQ, cucurbitadienol synthase; DDS, dammarenediol synthase; FRS, friedelin synthase; LUP, lupeol synthase; MRO, marneral synthase; MVA, mevalonate; P450s, cytochrome P450s; SC, squalene cyclase; SQE, squalene epoxidase; SQS, squalene synthase; THAS, thalianol synthase; UGTs, UDP-glycosyltransferases.

Figure 2.

Screenshot of the interactive phylogenetic tree containing all plant species included in the TriForC database. All triterpene enzymes produced by each of these plants and included in the TriForC database are linked to the respective plant name.

Figure 3.

Screenshot of the enzyme pages of the TriForC database. (A) The enzyme catalogue page shows for each enzyme the name, type, plant of origin, functional description and links to the GenBank accession number and the scientific paper describing it. The enzymes listed can also be restricted per enzyme type or plant species by clicking on one of the pop-up choices in the ‘Type’ or ‘Plant’ boxes on top. Every enzyme ‘line’ provides a link to a page devoted to one enzyme (B). The AaBAS enzyme page shows all available information for that enzyme as well as links to each compound page (substrates and products), pathways, host plant species, GenBank and UniProt accession numbers and scientific references (PubMed).

Figure 4.

Screenshots of some of the TriForC database tools. (A) Pathway section for Veratrum californicum. This scheme shows the complete triterpene biosynthesis pathway that is experimentally validated from this plant species. Full arrows correspond to established enzymatic reactions catalysed by identified and experimentally validated enzymes. Dashed arrows indicate that there is a putative intermediate compound between the substrate and product that still has not been experimentally isolated. (B) Substructure search tool. A carbon backbone with or without functional groups can be drawn in the designated area (left box). The search results display, simultaneously while drawing, the compounds present in the TriForC database that match the drawn structure.