A wide diversity of antifungal AMPs, produced by bacteria, are able to control fungal growth in vitro and in vivo. They mainly include antifungal AMPs produced by lactic acid bacteria (LAB), as well as species from the Streptomyces, Bacillus and Burkholderia genera, which are particularly active against fungal species belonging to the Aspergillus, Penicillium and Fusarium genera, but also to other species such as those from the Byssochlamys genus (Table 1). As examples of applications in vivo, the antifungal protein YvgO isolated from Bacillus thuringiensis, was able to extend the shelf-life of different fruit juices inoculated with the PAT producer Byssochlamys fulva, and provided a complimentary measure of protection in UV-treated fruit juices ^[35][77]. On the other hand, a high antifungal activity of peptides generated by L. plantarum TE10 was reported against A. flavus. Results demonstrated promising application of the peptide mixture as bio-control agent to prevent the growth of A. flavus in maize ^[36][78]. Relevant bacterial AMPs with effect on mycotoxin biosynthesis are highlighted in the next section.

Fungi have a complex repertoire of AFPs that differ in amino acid composition and sequence ^{[3][37][27][38][39]}[37,42,69,79,80]. Several studies already indicated that some of the most hazardous mycotoxin-producing fungi are sensitive to AFPs (Table 1). Of interest are those studies showing antifungal activity in a wide range of mycotoxin producers and differences in susceptibility to AFPs among the fungal genera and species. Delgado et al. ^[40][81] evaluated the antifungal activity of PgAFP from P. chrysogenum against toxigenic fungi commonly found in dry-ripened foods. PgAFP retarded the growth of most fungi tested and the main mycotoxin-producing fungi analyzed, such as those producing AFs (A. flavus and Aspergillus parasiticus), OTA (A. carbonarius, A. ochraceus, and P. nordicum), ST (A. versicolor) and PAT (P. expansum and P. griseofulvum). Recently, AFPs from P. digitatum (PdAfpB) and P. expansum (PeAfpA, PeAfpB and PeAfpC), were tested against a representative panel of mycotoxin-producing fungi belonging to the genera Alternaria, Aspergillus, Byssochlamys, Fusarium and Penicillium ^[41][82]. These were previously reported to produce up to 26 different mycotoxins. AFPs showed significant activity against most of the mycotoxigenic fungi tested, in particular PeAfpA. PeAfpC showed powerful inhibition against Byssochlamys spectabilis (PAT producer), which is an important spoilage fungus in pasteurized food products, such as fruit juices and canned fruits ^[42][83]. Differences in susceptibility to AFPs were observed among fungal genera. In general, Aspergillus, Byssochlamys and Penicillium were more sensitive than the Fusarium genus. Moreover, the antifungal effect of AFPs also differed within the same species ^[40][41][43][81,82,84]. Further studies on susceptibility and resistance of fungal species including more strains from each species are needed to elucidate antifungal specificities of AFPs.

Animal antifungal AMPs are produced at the sites that are constantly exposed to microbes, such as skin and mucosal barriers ^[109][149]. Various antifungal AMPs have been isolated from invertebrates and vertebrate species, including fish, amphibians, and mammals (Table 3). Several invertebrate AMPs display activity against mycotoxin-producing fungi, in particular Aspergillus and Fusarium species, and have been isolated from organisms such as scorpions, silk moth, fruit fly, mantis, bee, termites and ticks. Recently, the susceptibility of the AOH producer Alternaria brassicicola to thanatin, produced by the spined soldier bug Podisus maculiventris, was described ^[110][150]. An example of antifungal AMP from fish is pleurocidin, a cationic peptide isolated from the winter flounder Pleuronectes americanus, which showed antifungal activity against F. culmorum (DON, NIV and ZEA producer) and A. niger (OTA producer) ^[111][151]. Finally, mammalian antifungal AMPs are found in human and bovine, and show activity against a large list of mycotoxin-producing fungi including F. culmurum (DON, NIV, T-2 and ZON producer), P. expansum (PAT and CIT producer), A. niger (OTA producer), A. nidulans (ST), F. oxysporum (T-2 toxin, HT-2 toxin producer) and A. flavus (AFs producer).

Of note is the antifungal activity of the human β-defensin 3 (HBD-3) in cereal-based products. Application of 80 μg/mL delayed growth of F. culmorum, P. expansum and A. niger on bread after more than 13 days ^[112][152]. Antifungal functions of bovin lactoferrin and derived peptides have been also reported ^[113][114][153,154]. Different mycotoxin-producing fungi from Alternaria, Aspergillus, Penicillium and Fusarium were sensitive to lactoferrin-derived peptides. This report is interesting because lactoferrin has been designated by the United States Food and Drug Administration (FDA) as a GRAS food additive ^[115][155].

Plant AMPs are constitutively expressed in both plant storage and reproductive organs, but they can also be locally or systematically induced during plant defense response ^[72][113]. Antifungal AMPs have been isolated from a wide variety of plant species, and classified by amino acid sequence, position and number of cysteine residues involved in the disulfide bridges, and/or function to families ^[3][73][37,114]. A large list of these families show inhibitory activity against mycotoxin-producing fungi (Table 2). It is noteworthy that, contrary to that described for fungal AFPs, most fungi sensitive to plant antifungal AMPs are Fusarium species, especially F. culmurum, F. graminearum, F. oxysporum and F. solani. However, other toxigenic fungal species from Aspergillus (A. flavus, A. niger), Penicillium (P. expansum) and Alternaria (A. alternata, A. solani) have been successfully inhibited by antifungal AMPs from plants ^[3][74][73][37,43,114]. As a practical example, we highlight the application of the onion (Allium cepa) defensin Ace-AMP1on tomato leaves. Treated leaves showed enhance resistance to the tomato pathogen A. solani (TeA and AOH producer), making this AMP a promising fungicide to be used in agriculture ^[75][115] (Table 2).

The development of synthetic peptides has grown to overcome some drawbacks associated with natural peptides, including low antifungal activity, toxicity or instability. Synthetic AMPs that show antifungal properties against mycotoxin producers are listed in Table 4. This includes analogs of natural AMPs and de novo peptides together with information about the susceptible mycotoxin-producing fungi to these synthetic AMPs, which include different species from Aspergillus, Penicillium and Fusarium genera.

Different strategies have been employed for developing analogs of AMPs. Natural proteins and peptides can be used for the design of novel synthetic bioactive peptides that are more potent than the original ones. They can derive from natural cleavage of natural proteins such as LfcinB17-31 and LfcinB20-25, which are derived from bovine lactoferrin ^[114][154]. Another strategy is to use the sequence of natural occurring AMPs as a template and design a new molecule. For instance, it has been shown that one of the functional regions of defensins is primarily located in the C-terminal β-sheet domain, called the γ-core motif. This is the case of the γ-core motif of the tick selected defensins (DefMT3, DefMT6, and DefMT7), which enhanced antifungal activity against F. graminearum and F. culmorum ^[122][132][162,172]. Another extensively used method is based on designing peptides that changes positive charge. In the peptide AGM182 the second disulfide linkage of tachyplesin1 has been replaced by a sequence that assumes an amphipathic β-sheet conformation with maximized positive charge density ^[133][39].

In addition to these analogs of AMPs, many synthetic peptides have been constructed via de novo synthesis such as a group of peptides, named PAFs, which have been designed using a combinatorial library ^{[134][135][136]}[173,174,175]. Although these peptides were identified through a nonbiased approach, they show properties of natural AMPs. In fact, PAF26 has been proposed as a model peptide for the characterization and study of cationic, cell-penetrating antifungal peptides ^[137][176].

A good practical example of application is the tachyplesin1-derived peptide AGM182, which caused up to 72% reduction in A. flavus growth/infection after its expression in transgenic maize plants. Furthermore, reduced fungal growth in the AGM182 transgenic seeds resulted in a significant reduction in AF levels (76–98%) ^[138][31].