Convergence and divergence of bitterness biosynthesis and regulation in Cucurbitaceae

Abstract

Differentiation of secondary metabolite profiles in closely related plant species provide clues for unravelling biosynthetic pathways and regulatory circuits, an area that is still under-investigated. Cucurbitacins, a group of bitter and highly oxygenated tetracyclic triterpenes, are mainly produced by the plant family Cucurbitaceae. These compounds have similar structures, but differ in their anti-tumor activities and eco-physiological roles. By comparative analyses of the genomes of cucumber, melon, and watermelon, we uncovered conserved syntenic loci encoding metabolic genes for distinct cucurbitacins. Characterization of the cytochrome P450s (CYPs) identified from these loci enabled us to unveil a novel multi-oxidation CYP for the tailoring of the cucurbitacin core skeleton as well as two other CYPs responsible for the key structural variations among cucurbitacins C, B and E. We also discovered a syntenic gene cluster of transcription factors that regulate the tissue-specific biosynthesis of cucurbitacins and that may confer the loss of bitterness phenotypes associated with convergent domestication of wild cucurbits. This study illustrates the potential to exploit comparative genomics to identify enzymes and transcription factors that control the biosynthesis of structurally related yet unique natural products.

Metabolic GWAS‐based dissection of genetic bases underlying the diversity of plant metabolism

“…For instance, cucurbitacin C is only found in cucumber (Panosyan et al ., ), while cucurbitacins B and E are responsible for the bitterness of melon and watermelon, respectively (Da Costa and Jones, ; Shang et al ., ). A genetic study led to the characterization of the cytochrome P450s (CYPs) in conserved synthetic loci for the cucurbitacin core skeleton, while the loss of another CYP in melon and watermelon was found to be responsible for the species‐specific accumulation of cucurbitacin C (Zhou et al ., ). Recent research revealed that variation in metabolism within a species is much larger than that had previously been thought (Luo, ), which reflects genetic diversity determining natural occurring variation in metabolites.…”

“…To identify effects of more widespread genetic variants on metabolic diversity across natural populations, mGWAS was initially applied in the model species Arabidopsis thaliana and then successfully performed in and extended to a number of other species, especially important crops. These studies covered primary metabolites (Strauch et al ., ; Angelovici et al ., ; Du et al ., ) and secondary metabolites (Dong et al ., ; Peng et al ., , ), ranging from vegetative tissue (Chen et al ., ; Matsuda et al ., ; Fang et al ., ) to reproductive tissue (Wen et al ., ; Zhou et al ., ; Zhu et al ., ). Generally, agricultural performance is under the control of numerous loci of small effects (Huang et al ., ).…”

Gene Discovery in Gelsemium Highlights Conserved Gene Clusters in Monoterpene Indole Alkaloid Biosynthesis

“…Although plant genome data are becoming more readily available, we are still not able to predict which natural product pathways will be clustered and which will not. Moreover, although conserved gene clusters have been observed in closely related species that produce chemically similar products, it is not known how well gene clusters would be conserved in less closely related species that produce chemically divergent compounds. An example is the monoterpene indole alkaloids (MIAs), which are produced by plants of the Apocynaceae, Gelsemiaceae, Loganiaceae, Nyssaceae and Rubiaceae families.…”

Multi‐omics data‐driven investigations of metabolic diversity of plant triterpenoids

“…For tetracyclic terpene biosynthesis, CYP81Q58, CYP87D20, CYP88L2, CYP81Q59 and CYP87D18 are able to decorate the cucurbitadienol scaffold in the production of cucurbitacins and morgrol (Shang et al ., ; Itkin et al ., ; Zhou et al ., ). These enzymes, except for CYP81Q59 and CYP88L2, are conserved across the cucurbit plants.…”