Science 346, 1084–1088 (2014)

The bitter taste of cucumbers and squashes is due to cucurbitacins (CuCs), a class of triterpenoids involved in defence against herbivory. CuCs have been used in traditional medicine and possess cytotoxic and anticancer properties.

Yi Shang, of the Chinese Academy of Agricultural Sciences, and colleagues report a comprehensive genomic and biochemical study unravelling the pathway and regulatory mechanism underlying CuC biosynthesis. Through genome-wide association studies based on 115 cucumber lines, they mapped the previously reported Bi locus to the gene, Csa6G088690. Cucurbitadienol synthase activity of this gene was validated using yeast expression and gas chromatography–mass spectrometry assays. Analyses of mutants, gene expression patterns and genotype–phenotype association revealed two transcription factors, Bl (encoded by Csa5G156220) and Bt (Csa5G157230), binding to the Bi promoter, regulating its expression and, consequently, bitterness in leaves and fruits, respectively. Bt diversity has been reduced during the domestication of cucumbers, indicating that human selection has acted on this gene. A variation at Bt's promoter is critical for its expression under stress. The researchers identified seven cytochrome P450s and one acetyltransferase whose genes cluster or are co-expressed with Bi, and regulated by Bl and Bt, which catalyse three of the reactions converting cucurbitadienol to CuC.

Credit: © J. R. BALE/ALAMY

The CuC biosynthesis and regulatory networks, consisting of nine genes regulated by two transcription factors, could prove fertile ground for the engineering of anti-tumour drugs.