Steroidal scaffold decorations in Solanum alkaloid biosynthesis.

IF 17.1 1区 生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY
Molecular Plant Pub Date : 2024-08-05 Epub Date: 2024-06-26 DOI:10.1016/j.molp.2024.06.013
Rosalind Lucier, Mohamed O Kamileen, Yoko Nakamura, Sofiia Serediuk, Ranjit Barbole, Jens Wurlitzer, Maritta Kunert, Sarah Heinicke, Sarah E O'Connor, Prashant D Sonawane
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引用次数: 0

Abstract

Steroidal glycoalkaloids (SGAs) are specialized metabolites produced by hundreds of Solanum 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, α-solasonine and α-solamargine isolated from black nightshade (Solanum nigrum) are reported to have potent anti-tumor, anti-proliferative, and anti-inflammatory activities. Notably, α-solasonine and α-solamargine, along with the core steroidal aglycone solasodine, are the most widespread SGAs produced among the Solanum plants. However, it is still unknown how plants synthesize these bioactive steroidal molecules. Through comparative metabolomic-transcriptome-guided approach, biosynthetic logic, combinatorial expression in Nicotiana benthamiana, and functional recombinant enzyme assays, here we report the discovery of 12 enzymes from S. nigrum that converts the starting cholesterol precursor to solasodine aglycone, and the downstream α-solasonine, α-solamargine, and malonyl-solamargine SGA products. We further identified six enzymes from cultivated eggplant that catalyze the production of α-solasonine, α-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.

茄科生物碱生物合成中的类固醇支架装饰。
类固醇糖生物碱(SGAs)是由数百种茄科植物(包括番茄、马铃薯和茄子等重要蔬菜作物)产生的特殊代谢物。虽然 SGAs 因其在植物中的防御作用和对人类的 "抗营养 "作用(如毒性和苦味)而广为人知,但其中许多分子都具有抗癌、抗微生物、抗炎、抗病毒和抗发热等活性。其中,从黑夜来香(Solanum nigrum)中分离出的α-solasonine 和 α-solamargine据报道具有很强的抗肿瘤、抗增殖和抗炎活性。值得注意的是,α-茄红素和α-茄黄素以及核心甾类苷元索拉索定是茄科植物中最常见的 SGAs。然而,植物是如何合成这些具有生物活性的类固醇分子的仍是一个未知数。通过代谢组-转录组比较指导方法、生物合成逻辑、在烟花椰菜(Nicotiana benthamiana)中的组合表达以及功能重组酶测定,我们在此报告发现了 12 种来自黑茄科植物的酶,它们能将盯胆固醇前体转化为索拉索定苷醛酸,以及下游的 α-索拉索宁、α-索拉马金碱和丙二酰索拉马金碱 SGA 产物。我们进一步从栽培茄子中发现了 6 种酶,它们通过糖基化和非典型丙二酰化修饰,催化茄碱苷醛酸生成α-索拉索宁、α-索拉马吟和丙二酰索拉马吟 SGA。我们的工作为利用合成生物学在异源宿主中生产高价值甾体生物活性分子提供了基因工具箱和平台。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Molecular Plant
Molecular Plant 植物科学-生化与分子生物学
CiteScore
37.60
自引率
2.20%
发文量
1784
审稿时长
1 months
期刊介绍: Molecular Plant is dedicated to serving the plant science community by publishing novel and exciting findings with high significance in plant biology. The journal focuses broadly on cellular biology, physiology, biochemistry, molecular biology, genetics, development, plant-microbe interaction, genomics, bioinformatics, and molecular evolution. Molecular Plant publishes original research articles, reviews, Correspondence, and Spotlights on the most important developments in plant biology.
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