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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茄属生物碱生物合成中的类固醇支架装饰


甾体配糖生物碱 (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 在植物的防御和对人类的“抗营养”作用（例如毒性和苦味）方面发挥着重要作用，但其中许多分子已被证明具有抗癌、抗微生物、抗炎、抗衰老等作用。 -病毒和解热活性。其中，从黑龙葵中分离出来的 -solaso​​nine 和 -solamargine 据报道具有有效的抗肿瘤、抗增殖和抗炎活性。值得注意的是，-solaso​​nine 和 -solamargine 以及核心甾体苷元 solaso​​dine 是植物中产生最广泛的 SGA。然而，目前尚不清楚植物如何合成这些具有生物活性的甾体分子。通过比较代谢组学-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，我们在此报告发现了 12 种酶，可将起始胆固醇前体转化为 solaso​​dine 苷元，以及下游 -solaso​​nine、-solamargine、和丙二酰-solamargine SGA 产品。我们进一步从栽培茄子中鉴定出六种酶，这些酶催化从茄碱苷元通过糖基化和非典型丙二酰化修饰产生-茄茄碱、-茄茄碱和丙二酰-茄茄碱SGA。我们的工作提供了基因工具箱和平台，用于利用合成生物学在异源宿主中工程化生产高价值的甾体生物活性分子。