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During the past 30 yr an impasse has developed in the discovery and commercialization of synthetic herbicides with new molecular targets and novel chemistries. Similarly, there has been little success with bioherbicides, both microbial and chemical. These bioherbicides are needed to combat fast-growing herbicide resistance and to fulfill the need for more environmentally and toxicologically safe herbicides. In response to this substantial and growing opportunity, numerous start-up companies are utilizing novel approaches to provide new tools for weed management. These diverse new tools broaden the scope of discovery, encompassing advanced computational, bioinformatic, and imaging platforms; plant genome–editing and targeted protein degradation technologies; and machine learning and artificial intelligence (AI)-based strategies. This review contains summaries of the presentations of 10 such companies that took part in a symposium held at the WSSA annual meeting in 2024. Four of the companies are developing microbial bioherbicides or natural product–based herbicides, and the other six are using advanced technologies, such as AI, to accelerate the discovery of herbicides with novel molecular target sites or to develop non-GMO, herbicide-resistant crops.
Few herbicides with new molecular targets have been introduced in the past four decades (Duke and Dayan Reference Duke and Dayan2021). Before this drought in new modes of action (MOAs), a herbicide with a new MOA was introduced approximately every 3 yr (Gerwick Reference Gerwick2010). The last significant new MOA (hydroxyphenylpyruvate dioxygenase) was introduced in the 1980s. Since then, only two new MOAs (homogentisate solanesyltransferase and dihydroorotate dehydrogenase) from newly introduced herbicides have been added to the Herbicide Resistance Action Committee MOA classification scheme (HRAC 2024), represented by only two herbicides (cyclopyrimorate and tetflupyrolimet, respectively) (Kang et al. Reference Kang, Emptage, Kim and Gutteridge2023; Shino et al. Reference Shino, Hamada, Shigematsu and Banba2020), one of which (tetflupyrolimet) is not yet commercially available. Other new MOAs have been added to the HRAC classification scheme in recent years, but these have been the result of discovery of the MOAs of older herbicides for which the MOA was previously unknown, for example, proof that the MOA of endothall is the inhibition of serine/threonine protein phosphatase (Bajsa et al. Reference Bajsa, Pan, Dayan, Owens and Duke2012).
Due to the lack of novel classes of herbicides, the market is currently driven by a relatively small number of relatively old molecules. Moreover, some herbicides with MOAs discovered decades ago are increasingly being called into question because of environmental and toxicological issues. Consequently, the challenge is to go beyond developing analogues of chemical families with existing MOAs and find an entirely new generation of herbicides with novel MOAs. The question is how can a whole new generation of herbicides working in novel ways be found to tackle the drought in novel MOA discovery?
The evolution and spread of herbicide resistance have grown rapidly during the past few decades (Heap Reference Heap2024), increasing the need for herbicides with new chemistries to fight non–target site resistance and with new molecular targets to counter target-site resistance. Without effective herbicides, farmers can lose up to 40% of their crop yields from weed interference (Duke and Dayan Reference Duke and Dayan2021; Nickel and Polansek Reference Nickel and Polansek2024). The reasons for the dramatic decline in the introduction of much-needed herbicides with new MOAs are several, as discussed in detail by Duke and Dayan (Reference Duke and Dayan2021) and Powles (Reference Powles2023). One of the explanations for the dramatic decline in new herbicides is the diminishing returns with traditional chemical synthesis and screening of potentially herbicidal compounds. Similarly, in addition to the paucity of new herbicides with new MOAs, the introduction of significantly successful bioherbicides (both microbial bioherbicides and natural product–based herbicides) has been at a standstill for decades for different reasons than those of the attrition in introduction of new synthetic herbicides (Duke Reference Duke2024).
In the past decade, numerous small (start-up) companies have been formed that offer different approaches to herbicide and bioherbicide discovery (Dayan Reference Dayan2019). Powles (Reference Powles2023) mentions a dozen of these companies in a recent review, but there is no detailed information about their novel approaches to herbicide discovery or any of their discoveries. The present review is based on presentations from the ″‘New Approaches to Herbicide and Bioherbicide Discovery″ symposium organized during the 64th Annual Conference of the Weed Science Society of America (WSSA) held in San Antonio, TX. This symposium brought together speakers from 10 such companies with new approaches to herbicide and bioherbicide discovery. Summaries of their presentations are provided in the following sections.
