Czechowski Tomasz, Li Yi, Gilday Alison D, Harvey David, Swamidatta Sandesh H, Lichman Benjamin R, Ward Jane L, Graham Ian A
Centre for Novel Agricultural Products, Department of Biology, University of York, Heslington, York, YO10 5DD, UK.
Plant Sciences for the Bioeconomy, Rothamsted Research, Harpenden, AL5 2JQ, UK.
Nat Commun. 2025 Jul 1;16(1):5602. doi: 10.1038/s41467-025-60708-2.
Terpenoids are among the largest classes of plant natural products. Squalene, a high value commodity in the cosmetic, food and pharmaceutical industries, is a common linear precursor for the biosynthesis of C30 triterpenes and sterols across plant, animal and fungal kingdoms. The anti-fungal compound peplusol is another linear C30 triterpene, but has only been reported in the genus Euphorbia. Here, we show that peplusol production has evolved due to duplication of a sterol synthase gene with one copy acquiring peplusol synthase activity and the original gene retaining the ancestral function. We identify a number of key amino acid residues that can convert the squalene synthase enzyme into peplusol synthase and vice versa. The PEPLUSOL SYNTHASE gene from E. peplus is able to drive significant levels of peplusol production in alternate host production platforms including Nicotiana benthamiana (over 2.5% leaf dry weight) and Saccharomyces cerevisiae (30 mg/L culture).
萜类化合物是植物天然产物中最大的类别之一。角鲨烯是化妆品、食品和制药行业中的高价值商品，是植物、动物和真菌界中C30三萜和甾醇生物合成的常见线性前体。抗真菌化合物peplusol是另一种线性C30三萜，但仅在大戟属中被报道过。在这里，我们表明peplusol的产生是由于一个甾醇合酶基因的复制，其中一个拷贝获得了peplusol合酶活性，而原始基因保留了祖先功能。我们鉴定出了一些关键氨基酸残基，它们可以将角鲨烯合酶转化为peplusol合酶，反之亦然。来自peplus大戟的PEPLUSOL合酶基因能够在包括本氏烟草（超过2.5%的叶片干重）和酿酒酵母（30mg/L培养物）在内的替代宿主生产平台中驱动显著水平的peplusol产生。
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