# Natural Salicylaldehyde for Fungal and Pre- and Post-Emergent Weed Control
###### Abstract
Therefore, the development of a new, sustainable weed control system or formulation that can be applied as safe alternatives to conventional, toxic herbicides is continually needed. Despite this need, the development of entirely new herbicides is a very expensive and time-consuming process. While there has been a steady increase in the numbers of herbicide-resistant weeds in the fields, no new herbicide modes of action have been identified or introduced to the market in 30 years [10]. We investigate a fast pesticide screening system to expedite the identification of new, safe pesticide alternatives or intervention strategies. One of the approaches is drug/chemical repurposing [11], which is the repositioning of already marketed drugs or chemicals previously developed for treating human diseases/pathogens or as food additives to treat new types of problems such as weed invasion. The advantage of the repurposing approach is that the mechanism of action, cellular targets, toxicity profile, or safety of the repurposed drugs/chemicals have already been identified and documented, thus accelerating the regulatory approval following the repurposing. We previously identified via repurposing that salicaldehyde (SA; 2-hydroxybenzaldehyde) exerted a potent anti-aflatoxigenic and antifungal activity as a fumigant [12; 13]. SA is a natural, redox-active small molecule listed as a Generally Recognized As Safe agent by the EFSA [14] and the United States Food and Drug Administration (FDA) [15] that has been used in the drug/food industries as an intermediate for pharmaceuticals or a food-flavoring agent. Meanwhile, agricultural industries produce an excess of byproducts/biomass of crops annually. For example, tree nuts (almonds, walnuts, pistachios) are the largest commodity produced in California, United States [16], which results in the excess production of agricultural byproducts such as nutshells and hulls each year. Considering tree nuts also capture and store a huge amount of carbon over their life cycle, effective utilization of the byproducts is one of the key components to reducing carbon emissions (thus, carbon sequestration). Therefore, finding effective ways to manage agricultural byproducts is of high importance [17; 18]. Currently, orchard recycling, namely, byproduct incorporation back into the orchard soil, is one of the compelling alternative methods to managing agricultural byproducts. However, since agricultural byproducts are commonly contaminated with environmental fungal and bacterial pathogens, it is critical to ensure that byproducts do not harm soil health or integrity by passing along pathogens, especially those resistant to conventional antibiotics/fungicides or producing mycotoxins, during field application (orchard recycling). Of note, the fumigant SA emitted from the delivery vehicles not only inhibited the production of aflat B and G (AFB1, AFB2, AFG1, AFG2) by _Aspergillus flavus_ and _Aspergillus parasitic_ (Figure S2) but also prevented the growth of fungal pathogens [12; 13]. Fungal mutants lacking genes in the antioxidant system (such as superoxide dismutase and glutathione reductase) were highly susceptible to the treatment, indicating that SA interferes with cellular redox homeostasis in fungi [12; 13]. The intrinsic anti-aflatoxigenic and antifungal activity of SA as a fumigant are well-suited for sanitation practices in crop fields, especially during agricultural byproduct recycling in tree nut orchards. In this proof-of-concept investigation, the following was performed: (1) repurposing the natural food additive SA as a pre- and post-emergent weed control agent, (2) developing tree nutshell particles as SA delivery vehicles for use in orchards, thus integrating into the growers' sustainable byproduct recycling program, and (3) determining soil covering/pasteurization as one of the optimum practices to effectively deliver SA to the soil.