## 2 Challenges Associated with Isolating Microbial Biocontrols  
Microbial biocontrol has proven to be a technique with a broad activity spectrum against various pathogens and pests [7]. Microbial biocontrol can support plant growth, enhance stress tolerance, support plant nutrition, and antagonize plant pathogens (Figure 1) [8]. The need to sustainably intensify agricultural productivity using endophytic research to combat biotic (pathogens and pests) and abiotic stresses has inherent challenges due to the complexity of microbiomes associated with plants. Hence, the Integration of plant biocontrol agents is an efficient approach that presents a promising solution for boosting agricultural productivity. However, the efficient commercial use of endophytic organisms as biocontrol agents or growth promoters would require addressing several challenges associated with isolating these microorganisms. Therefore, the use of novel isolation and screening approaches are required to obtain native microbial biocontrol with effective antagonistic activity. The development of these isolation and screening approaches is often driven to solve a certain threat to agricultural productivity [9]. One of the challenges associated with isolating different microbial biocontrol candidates is mycotoxin contamination [10]. However, mycotoxin detoxification, transformation and adsorption can reduce mycotoxin contamination in the form of yeast, bacteria, fungi and enzymes [11]. These agents can degrade or adsorb mycotoxins before their direct destructive effect on the harvest. Nevertheless, these strategies are affected by environmental factors during interactions, and thus there is an increasing risk of sexual recombination between toxigenic lines and microbial biocontrol strains. This occurrence eventually leads to the emergence of hypervirulent toxigenic strains. Thus, to address this problem, characterization of microbial biocontrol agents at genus level, using sensitive methods, are required for better functional characterization at species level to address this problem [12]. Bio-detoxification of mycotoxins using probiotic lactic acid bacteria has effectively removed contaminants by biodegradation or bio-adsorption pathways [13]. Bio-adsorption involvesdirect binding of the toxin to the bacteria, in which binding is affected by the bacterial affinity toward the toxin [14]. However, biodegradation, which is more durable and irreversible compared to bio-adsorption, can modify toxin structure and result in unwanted metabolites (such as aflatoxin from aflatoxin B1), which could be detrimental to the host [15], thus in itself reducing the implementation or opportunity for natural biocontrol adaptation. Another challenge of microbial biocontrol agents is the antagonistic mechanisms that control or suppress pathogens and their intricate interactions among the host, pathogen, and the environment. These interactions can be affected by multiple factors which include the environmental conditions and the presence of microbial colonizers in the biological system [16]. However, intensified efforts toward a better understanding of the mechanism and mode of actions in the area of direct antibiosis, hyperparasitism, induction of resistance and competition for space and nutrients would facilitate the optimization of control and allow the use of more efficient strains in the correct environment [17]. The use of microbial biocontrol agents within the agriculture industry hinges on the regularization and commercialization of the microorganisms while allowing them to still remain competitive with synthetic chemical pesticides and fumigants [18]. It is also expedient to evaluate the toxicology of these agents [19], while bold efforts should be made toward proper preservation methods and commercial-scale production strategies [20]. The Use of the CRISPR/Cas9 System in Endophytic Research for Enhanced Biocontrol or Improved Plant Growth  
Genome editing research underwent a re-emergence with the development of the CRISPR/Cas9 system [21].