PROTAC for agriculture: learning from human medicine to generate new biotechnological weed control solutions
PROTAC for agriculture: learning from human medicine to generate new biotechnological weed control solutions
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PROTAC 用于农业：学习人类医学以产生新的生物技术杂草控制解决方案
DOI：
10.1002/ps.7741
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发表时间：
2023
影响因子：
4.1
通讯作者：
Bassham, Diane C.
中科院分区：
文献类型：
--
作者：
Leon, Ramon G.;Bassham, Diane C.
近一个世纪以来，杂草控制一直依赖于使用干扰药物靶标（尤其是酶）的有机和无机分子。这种方法虽然有效，但已导致多起除草剂抗药性案例。此外，选择性且具有有利环境特征的新药物靶点的发现速度已经放缓，凸显了对创新控制工具的需求。生物技术和基因组学时代的到来给许多人带来了希望，即各种新的控制工具将会被开发出来。然而，现实情况是，大多数努力仅限于开发对少数现有除草剂具有抗性的转基因作物，这实际上只是另一种形式的选择性。蛋白水解靶向嵌合体（PROTAC）是一种为治疗人类疾病而开发的新技术，但在农业中具有多种应用潜力。该技术使用与 E3 配体连接的小诱饵分子。诱饵的 3 维结构有利于与目标蛋白中的结合位点发生物理相互作用，从而允许 E3 募集、泛素化，然后进行蛋白酶体介导的降解。该系统可以避免寻找可成药靶点的需要，因为它可以降解结构蛋白、转运蛋白、转录因子和酶，而不需要与活性位点相互作用。 PROTAC 可以帮助控制抗除草剂杂草，并扩大可用于杂草控制的生化靶点的数量。在本文中，我们概述了 PROTAC 的工作原理，并描述了杂草控制的可能应用以及该技术在开发和现场使用过程中可能面临的挑战。 © 2023 The Authors.Pest Management Science 由 John Wiley & Sons Ltd 代表化学工业协会出版。
Weed control has relied on the use of organic and inorganic molecules that interfere with druggable targets, especially enzymes, for almost a century. This approach, although effective, has resulted in multiple cases of herbicide resistance. Furthermore, the rate of discovery of new druggable targets that are selective and with favorable environmental profiles has slowed down, highlighting the need for innovative control tools. The arrival of the biotechnology and genomics era gave hope to many that all sorts of new control tools would be developed. However, the reality is that most efforts have been limited to the development of transgenic crops with resistance to a few existing herbicides, which in fact is just another form of selectivity. Proteolysis‐targeting chimera (PROTAC) is a new technology developed to treat human diseases but that has potential for multiple applications in agriculture. This technology uses a small bait molecule linked to an E3 ligand. The 3‐dimensional structure of the bait favors physical interaction with a binding site in the target protein in a manner that allows E3 recruitment, ubiquitination and then proteasome‐mediated degradation. This system makes it possible to circumvent the need to find druggable targets because it can degrade structural proteins, transporters, transcription factors, and enzymes without the need to interact with the active site. PROTAC can help control herbicide‐resistant weeds as well as expand the number of biochemical targets that can be used for weed control. In the present article, we provide an overview of how PROTAC works and describe the possible applications for weed control as well as the challenges that this technology might face during development and implementation for field uses. © 2023 The Authors.Pest Management Sciencepublished by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.