Limonoids on the menu.
Limonoids on the menu.
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菜单上有柠檬苦素。
DOI：
10.1038/s41589-023-01287-5
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发表时间：
2023
影响因子：
14.8
通讯作者：
De Mattos-Shipley K
中科院分区：
文献类型：
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作者：
De Mattos-Shipley K
limestone是由芸香科（柑橘）和楝科（桃花心木）的成员产生的三萜类植物化学物质，其表现出丰富的有吸引力的生物活性，包括抗癌、抗炎、抗HIV和杀虫活性。它们的复杂性使得化学合成非常困难，这限制了它们的潜在用途，因为它们可以很容易地从植物中提取。为了揭示它们的生物合成途径并为可持续生产开辟道路，De La Peña等人对柑橘和苦楝进行了广泛的转录组和基因组挖掘，候选酶在本氏烟草中异源表达，揭示了它们的催化作用，并导致了两种柠檬苦素类化合物的完全生物合成：azadirone和kihadalactone A。总共鉴定了22个柠檬苦素生物合成基因，其编码12种不同的化学转化，包括支架重排、乙酰化和各种氧化。甾醇异构酶已被证明是从初级代谢中招募和适应的，并且已被证明通过C-4部分的氧化裂解来安装签名呋喃环，揭示了植物中呋喃形成的新机制。这项工作中揭示的代谢网络不仅扩大了对三萜类化合物生物合成的理解，而且还将明显加速柠檬苦素类化合物的研究领域，并通过提供更容易获得的多种生物活性化合物为其未来的应用奠定基础。
Limonoids are triterpenoid phytochemicals made by members of the Rutaceae (citrus) and Meliaceae (mahogany) families that exhibit a wealth of attractive bioactivities, including anti-cancer, anti-inflammatory, anti-HIV and insecticidal activities. Their complexity makes chemical synthesis extremely difficult, which currently limits their potential utility to compounds that can be easily extracted from plants. To uncover their biosynthetic pathway and unlock avenues for sustainable production, De La Peña et al. conducted an extensive program of transcriptome and genome mining from Citrus sinensisand Melia azedarach.Candidate enzymes were heterologously expressed in Nicotiana benthamiana, which uncovered their catalytic roles and led to the total biosynthesis of two limonoids: azadirone and kihadalactone A. In total, 22 limonoid biosynthetic genes were identified, which encoded 12 distinct chemical transformations, including scaffold rearrangements, acetylations and various oxidations. Sterol isomerases were shown to have been recruited and adapted from primary metabolism, and the signature furan ring was shown to be installed via oxidative cleavage of a C-4 moiety, uncovering a new mechanism for furan formation in plants. The metabolic network revealed in this work not only expands the understanding of triterpenoid biosynthesis but will also undoubtably accelerate the field of research into limonoids, and could lay the foundation for their future use by providing easier access to diverse bioactive compounds.