Steroidal glycoalkaloids (SGAs) are specialized metabolites produced by hundreds of species, including important vegetable crops such as tomato, potato, and eggplant. Although it has been known that SGAs play important roles in defense in plants and “anti-nutritional” effects (e.g., toxicity and bitterness) to humans, many of these molecules have documented anti-cancer, anti-microbial, anti-inflammatory, anti-viral, and anti-pyretic activities. Among these, -solasonine and -solamargine isolated from black nightshade () are reported to have potent anti-tumor, anti-proliferative, and anti-inflammatory activities. Notably, -solasonine and -solamargine, along with the core steroidal aglycone solasodine, are the most widespread SGAs produced among the plants. However, it is still unknown how plants synthesize these bioactive steroidal molecules. Through comparative metabolomic-transcriptome-guided approach, biosynthetic logic, combinatorial expression in , and functional recombinant enzyme assays, here we report the discovery of 12 enzymes from that converts the starting cholesterol precursor to solasodine aglycone, and the downstream -solasonine, -solamargine, and malonyl-solamargine SGA products. We further identified six enzymes from cultivated eggplant that catalyze the production of -solasonine, -solamargine, and malonyl-solamargine SGAs from solasodine aglycone via glycosylation and atypical malonylation decorations. Our work provides the gene tool box and platform for engineering the production of high-value, steroidal bioactive molecules in heterologous hosts using synthetic biology.

中文翻译：

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Solanum 生物碱生物合成中的甾体支架装饰


甾体甾醇甙生物碱 （SGA） 是由数百个物种产生的特殊代谢物，包括番茄、马铃薯和茄子等重要蔬菜作物。尽管众所周知，SGA 在植物防御和对人类的“抗营养”作用（例如，毒性和苦味）中起着重要作用，但其中许多分子已经记录了抗癌、抗微生物、抗炎、抗病毒和解热活性。其中，据报道，从黑龙葵 （） 中分离的 -solasonine 和 -solamargine 具有强大的抗肿瘤、抗增殖和抗炎活性。值得注意的是，-solasonine 和 -solamargine 以及核心甾体糖苷配基 solasodine 是植物中产生的最广泛的 SGA。然而，植物如何合成这些生物活性甾体分子仍然未知。通过比较代谢组转录组指导的方法、生物合成逻辑、组合表达和功能重组酶测定，我们在这里报告了 12 种酶的发现，这些酶将起始胆固醇前体转化为索拉索定糖苷配基，以及下游 - 大豆苷、-大豆苷和丙二酰 - 大豆苷 SGA 产物。我们进一步从培养的茄子中鉴定了六种酶，它们通过糖基化和非典型丙二酰化修饰从索索定糖苷配基中催化 -索拉索宁、-索拉margine 和丙二酰-索拉索尔基 SGA。我们的工作为使用合成生物学在异源宿主中设计生产高价值的甾体生物活性分子提供了基因工具箱和平台。