Herbicidal Active Compound Ferulic Acid Ethyl Ester Affects Fatty Acid Synthesis by Targeting the 3-Ketoacyl-Acyl Carrier Protein Synthase I (KAS I)

Abstract

Exploring new herbicide targets based on natural product derivatives is an important research aspect for the generation of innovative pesticides. Ferulic acid ethyl ester (FAEE), a natural product derivative from ferulic acid, has significant herbicidal activity mainly by inhibiting the normal growth of weed seedling roots. However, the FAEE target protein underlying its herbicidal activity has not been identified. In this study, we synthesized an FAEE probe to locate its site of action. We discovered that FAEE entry point was via the root tips. Fourteen major binding proteins were identified using Drug affinity responsive target stability (DARTS) combined with LC-MS/MS, which included 3-ketoacyl-acyl carrier protein synthase I (KAS I) and phenylalanine ammonia-lyase I (PAL I). The KAS I and PAL I proteins/genes expression was changed significantly after exposure to FAEE, as evidenced by combined transcriptomic and proteomic analysis. A molecular docking assay indicated that KAS I and FAEE had a strong binding ability. Combined with previous studies on FAEE mechanism of action, and based on our results, we conclude that FAEE targeting KAS I lead to the blockage of the fatty acid synthesis pathway and result in plant death.

Discovery of Novel Pyrazole Acyl Thiourea Skeleton Analogue as Potential Herbicide Candidates

“…8,9 Moreover, several potential herbicide targets and their lead structures have been reported. These include halogenated 5-(2-hydroxyphenyl)pyrazoles as pseudilin analogues targeting the enzyme IspD in the methylerythritol phosphate pathway, 10 INH1 as a potential SNF1-related protein kinase 2 inhibitor for regulating abiotic stress responses and development, 11 ferulic acid ethyl ester potentially targeting the 3-ketoacyl−acyl carrier protein synthase I to interfere with the fatty acid synthesis pathway, 12 and transketolase (TKL), located in both the Calvin cycle and the oxidative pentose phosphate pathway, along with its potential herbicidal activity inhibitor cornexistin, 13,14 and many others. 15 Rational molecular design approaches in pharmaceutical and agrochemical studies, in conjunction with structure−activity relationship studies, can facilitate lead scaffold optimization, thereby enabling the development of novel compounds with intellectual property rights.…”

“…To date, over 20 specific protein targets have been identified for approved herbicides, encompassing processes such as photosynthesis, cellular metabolism, cell division, and growth. , Moreover, several potential herbicide targets and their lead structures have been reported. These include halogenated 5-(2-hydroxyphenyl)­pyrazoles as pseudilin analogues targeting the enzyme IspD in the methylerythritol phosphate pathway, INH1 as a potential SNF1-related protein kinase 2 inhibitor for regulating abiotic stress responses and development, ferulic acid ethyl ester potentially targeting the 3-ketoacyl–acyl carrier protein synthase I to interfere with the fatty acid synthesis pathway, and transketolase (TKL), located in both the Calvin cycle and the oxidative pentose phosphate pathway, along with its potential herbicidal activity inhibitor cornexistin, , and many others …”

Synthesis, biological evaluation, and molecular docking of novel ferulic acid derivatives containing a 1,3,4-oxadiazole thioether and trifluoromethyl pyrimidine skeleton

“… 5–8 Among them, ferulic acid is a natural plant metabolite that is usually found in Ferula assa-foetida L., Ligusticum chuanxiong Hort., Catalpa ovata G. Don 9 and so on. Ferulic acid is a phenylpropanoid natural product containing a phenolic hydroxyl group and has a great variety of pharmacological activities, such as herbicidal, 10,11 fungicidal, 12,13 antiviral, 14,15 and bactericidal 16–18 activities. Therefore, ferulic acid derivatives are a class of lead compounds designed and synthesized for new pesticides.…”