Duke Stephen O, Pan Zhiqiang, Bajsa-Hirschel Joanna
National Center for Natural Products Research, School of Pharmacy, University of Mississippi, Oxford, MS 38655, USA.
Natural Products Utilization Research Unit, Agricultural Research Service, United States Department of Agriculture, Oxford, MS 38655, USA.
Plants (Basel). 2020 Dec 11;9(12):1756. doi: 10.3390/plants9121756.
Knowledge of the mode of action of an allelochemical can be valuable for several reasons, such as proving and elucidating the role of the compound in nature and evaluating its potential utility as a pesticide. However, discovery of the molecular target site of a natural phytotoxin can be challenging. Because of this, we know little about the molecular targets of relatively few allelochemicals. It is much simpler to describe the secondary effects of these compounds, and, as a result, there is much information about these effects, which usually tell us little about the mode of action. This review describes the many approaches to molecular target site discovery, with an attempt to point out the pitfalls of each approach. Clues from molecular structure, phenotypic effects, physiological effects, omics studies, genetic approaches, and use of artificial intelligence are discussed. All these approaches can be confounded if the phytotoxin has more than one molecular target at similar concentrations or is a prophytotoxin, requiring structural alteration to create an active compound. Unequivocal determination of the molecular target site requires proof of activity on the function of the target protein and proof that a resistant form of the target protein confers resistance to the target organism.
了解化感物质的作用模式可能因多种原因而具有重要价值，例如证明和阐明该化合物在自然界中的作用以及评估其作为农药的潜在效用。然而，发现天然植物毒素的分子靶位点可能具有挑战性。因此，我们对相对较少的化感物质的分子靶标了解甚少。描述这些化合物的次生效应要简单得多，结果是有很多关于这些效应的信息，但这些信息通常很少能告诉我们其作用模式。本综述描述了发现分子靶位点的多种方法，并试图指出每种方法的陷阱。讨论了来自分子结构、表型效应、生理效应、组学研究、遗传学方法以及人工智能应用的线索。如果植物毒素在相似浓度下有多个分子靶标，或者是一种前植物毒素，需要进行结构改变以产生活性化合物，那么所有这些方法都可能会混淆。明确确定分子靶位点需要证明对靶蛋白功能有活性，以及证明靶蛋白的抗性形式赋予靶标生物抗性。
