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. 2026 Oct 1;42(5):726–737. doi: 10.5423/PPJ.OA.08.2026.0108

Secondary Metabolites from the Marine-Derived Fungus Aspergillus udagawae SFC20170619-M03 Exhibiting Disease Control Activity

Minh Van Nguyen 1, Jae Woo Han 1,2, Huisoo Cho 1,3, Myung Soo Park 4, Gyung Ja Choi 1,2,*, Hun Kim 1,2,*
PMCID: PMC13655606  PMID: 42860789

Abstract

In our screening program for novel biocontrol agents, we found that the culture filtrate of the marine-derived fungus Aspergillus udagawae SFC20170619-M03 exhibited disease control activity against several fungal plant diseases, including tomato gray mold, tomato late blight, and pepper anthracnose. Bioassay-guided fractionation of the active extracts led to the isolation of sixteen secondary metabolites, comprising nine xanthones (1–9), three benzoquinones (10–12), three spirocyclic furanone lactams (13–15), and one polyene (16). Among these compounds, the xanthone derivative MS-347a (1), a principal bioactive metabolite of A. udagawae SFC20170619-M03, exhibited promising antifungal and antibacterial activities, with minimum inhibitory concentrations ranging from 3.2 to 100 μg/mL. In planta assays further demonstrated that MS-347a (1) effectively suppressed tomato gray mold, tomato late blight, and pepper anthracnose, with control efficacies from 55% to 94% at a concentration of 62.5 μg/mL. The non-epoxidized xanthone AGI-B4 (7) exhibited potent and selective anti-oomycete activity against Phytophthora infestans, with a control efficacy of 91% against tomato late blight at 500 μg/mL. The benzoquinone derivative fumigatin (10) exhibited relatively weaker but broader-spectrum antimicrobial activity in vitro and provided moderate suppression of tomato gray mold in vivo. Taken together, these findings suggest that A. udagawae SFC20170619-M03 and its bioactive metabolites represent promising resources for the development of environmentally sustainable biocontrol agents for agricultural applications.

Keywords: Aspergillus udagawae, antimicrobial, plant disease control, quinone, xanthone

The increasing global population, disruptions in food production chains, and the prevalence of plant diseases continue to influence global food security (Gai and Wang, 2024). Chemical pesticides have long been used as effective strategies for controlling plant diseases and enhancing crop productivity (Waard et al., 1993). However, the repeated and prolonged use of synthetic pesticides has driven the gradual adaptation of plant pathogens, leading to reduced efficacy (Fisher et al., 2018). Resistance of plant pathogens to chemical pesticides has been reported in several major crops, including wheat, rice, maize, potato, and soybean, contributing to significant yield losses in various agricultural systems (Yin et al., 2023). In addition, excessive use of chemical pesticides has raised significant concerns regarding adverse effects on ecosystem, animals, and human health (Zhou et al., 2025). Despite these concerns, synthetic pesticides remain widely used in agriculture due to their rapid efficacy, scalability, and well-established application practices (Waard et al., 1993). To mitigate these concerns, alternative strategies aimed at reducing dependence on chemical pesticides have been actively explored. Nature-derived products have attracted attention as promising candidates for plant disease management. Several antibiotics derived from microorganisms, such as blasticidin and kasugamycin, have been identified and applied for disease control in crops (Copping and Duke, 2007). Therefore, expanding the chemical and functional diversity of antimicrobial natural products is essential to address the inherent limitations of naturally derived agents and to enable the development of effective, scalable, and sustainable alternatives for plant disease management (Rodrigo et al., 2022).

Aspergillus species, particularly toxigenic strains within section Flavi, such as Aspergillus flavus, are well-known plant pathogens due to their production of mycotoxins, including aflatoxins, which threaten agriculture and mammalian health (Amaike and Keller, 2011). In contrast, atoxigenic Aspergillus strains have shown considerable potential as biocontrol agents, offering a sustainable approach to mitigating mycotoxin contamination and controlling plant diseases (Ehrlich, 2014). These strains employ diverse mechanisms, including the production of bioactive metabolites (e.g., secondary metabolites and volatile organic compounds), secretion of hydrolytic enzymes, competition for space and nutrients, and induction of host plant resistance (Atallah and Yassin, 2020; Ehrlich, 2014; Lavkor et al., 2023; Wang et al., 2024). Notably, Aspergillus species are recognized as prolific sources of structurally diverse metabolites with broad biological activities (El-Hawary et al., 2020; Vadlapudi et al., 2017; Wang et al., 2024). Representative compounds include averythrin, fumitremorgin B, verruculogen, fonsecinone A, and metabolites from marine-derived Aspergillus spp., which have demonstrated antimicrobial activity against various phytopathogens (Li et al., 2012; Liu et al., 2014; Xiao et al., 2014). In addition, oxalic acid produced by Aspergillus niger has been reported to suppress bacterial fruit blotch on watermelon and exhibit nematicidal activity against Meloidogyne incognita (Gao et al., 2017; Jang et al., 2016). These findings highlight the potential of Aspergillus-derived metabolites as sources of antimicrobial agents for plant disease management.

As part of ongoing efforts to identify marine microorganisms as sources of biocontrol agents, we found that the culture filtrate of the marine-derived fungus Aspergillus udagawae SFC20170619-M03 exhibits activity against several fungal plant diseases. In this study, we focused on the isolation and structural characterization of secondary metabolites responsible for the antifungal activity of A. udagawae SFC20170619-M03, together with evaluations of their in vitro and in vivo antifungal activities. These findings provide a scientific basis for the development of environmentally sustainable alternatives to conventional synthetic agrochemicals.

Materials and Methods

Microbes and culture conditions

A. udagawae SFC20170619-M03, isolated from the west coast of South Korea (37°36’36.3”N, 126°31’13.8”E), was kindly provided by the Marine Bio-Resource Information System (https://www.mbris.kr). To investigate the secondary metabolites produced by A. udagawae SFC20170619-M03, twenty agar plugs that were punched with a six mm-diameter cork-borer from culture plates were inoculated into a 2 L Erlenmeyer flask containing 400 mL of potato dextrose broth (PDB; BD Difco, San Jose, CA, USA) and incubated at 25°C for 14 days. For the antimicrobial activity assay, fungal pathogens were obtained from the Korean Agricultural Culture Collection (https://genebank.rda.go.kr), as listed in Supplementary Table 1. The fungal strains were maintained on potato dextrose agar (PDA) medium at 25°C, except for Botrytis cinerea and Phytophthora infestans, which were cultured at 20°C. The bacterial pathogens were kindly provided by the Rural Development Administration (Wanju, Korea) (Supplementary Table 1), which were maintained on tryptic soy agar (TSA; BD Difco). Pseudomonas syringae pv. actinidiae and Xanthomonas arboricola pv. pruni were grown at 25°C and all other strains were cultured at 30°C.

General experimental procedures for chemical analysis

Analytical thin-layer chromatography (TLC) was performed on silica gel 60 F245 and RP–18 F245S plates (Kiesel gel 60, 20 × 20 cm, 0.25 mm thickness; Merck & Co., Inc., Kenilworth, NJ, USA). Spots were visualized under UV light and by spraying with p-anisaldehyde reagent. Medium-pressure liquid chromatography was performed using an Isolera One system (Biotage, Uppsala, Sweden) equipped with Biotage cartridges. Preparative high-performance liquid chromatography (HPLC) was performed on an LC-20AR HPLC system (Shimadzu, Kyoto, Japan) equipped with a YMC C18 column (20 × 250 mm i.d., 5 μm). All solvents were purchased from Samchun Pure Chemical Co., Ltd. (Seoul, Korea) and used without further purification. One- and two-dimensional nuclear magnetic resonance (1D and 2D NMR) spectra were recorded on a Bruker Advance 400 MHz spectrometer (Bruker Co., Billerica, MA, USA). High-resolution electrospray ionization mass spectrometry (HRESIMS) data were acquired using a SYNAPT G2 instrument (Waters Co., Milford, MA, USA).

Extraction and isolation of the active compounds from A. udagawae SFC20170619-M03

The extraction and isolation scheme of secondary metabolites from the fungus A. udagawae SFC20170619-M03 is summarized in Supplemental Fig. 1. The fungus was cultured in PDB medium at 25°C with shaking at 160 rpm for 14 days. The entire culture broth (9.6 L) was filtered to separate the culture filtrate from the fungal biomass. The culture filtrate was successively partitioned three times with equal volumes of ethyl acetate (EtOAc) and then twice with an equal volume of n-butanol (BuOH). The EtOAc and BuOH layers and the residual aqueous phase were concentrated to dryness, yielding the CF-E (8.0 g), CF-B (2.4 g), and CF-W (20.0 g), respectively. The mycelial mass was extracted with acetone (2 L) by sonication for 30 min and maceration overnight at room temperature. After filtration, the acetone was removed under reduced pressure, and the resulting mycelial extract was subjected to the same partitioning procedure, yielding the ME-E (10.8 g), ME-B (1.4 g), and ME-W (5.0 g) extracts.

The active CF-E extract (8.0 g) was subjected to silica gel column chromatography (200 mL column volume) and eluted with a gradient of methanol (MeOH) in chloroform (CHCl3) at a flow rate of 50 mL/min, yielding compound 10 (250.0 mg) and three fractions (E-2 to E-4) based on TLC analysis. Fraction E-2 (5.2 g) was further separated on an MCI column using a gradient of MeOH in water (10% to 100%, v/v), affording compounds 12 (366.1 mg), 11 (203.9 mg), 2 (218.8 mg), and 16 (64.8 mg), together with subfraction E-27 (1.4 g). Subfraction E-27 was purified by preparative HPLC using 38% (v/v) MeOH in water containing 0.1% (v/v) formic acid at a flow rate of 5.0 mL/min to yield compounds 7 (50.0 mg), 8 (30.0 mg), and fraction E-273 (300 mg). Fraction E-273 was further purified by preparative HPLC under isocratic conditions with 35% (v/v) acetonitrile in water at a flow rate of 5.0 mL/min to afford compounds 13 (5.6 mg), 14 (3.2 mg), 9 (10.1 mg), and fraction E-2734 (15.0 mg). Fraction E-2734 was finally purified by preparative TLC using CHCl3–MeOH (15:1, v/v) as the developing solvent, yielding compound 15 (2.2 mg).

The active ME-E extract (10.8 g) was chromatographed on a silica gel column (500 mL column volume) using a gradient of MeOH in CHCl3 at a flow rate of 50 mL/min, yielding five fractions (ME-1 to ME-5). Fraction ME-3 was further separated using a SNAP KP-Sil 50 g cartridge with a gradient of 0–50% (v/v) EtOAc in dichloromethane, affording compound 1 (853.0 mg) and three fractions (ME-31 to ME-33). Fractions ME-32 and ME-33 were combined and then purified by preparative HPLC using a gradient of MeOH in water containing 0.1% (v/v) formic acid at a flow rate of 5.0 mL/min to yield compounds 3 (0.8 mg), 4 (7.4 mg), 5 (1.1 mg), and 6 (1.4 mg).

Microdilution broth assay

Minimum inhibitory concentration (MIC) values of the sixteen purified compounds against eight phytopathogenic fungi and twelve phytopathogenic bacteria were determined using a broth microdilution assay with twofold serial dilutions (Nguyen et al., 2022). Briefly, fungal spore (1 × 105 spores/mL) and bacterial cell suspensions (1 × 105 CFU/mL) prepared in the PDB and tryptic soy broth (BD Difco) medium, respectively, and then were dispensed into 96-well microtiter plates. Stock solutions of the test compounds dissolved in dimethyl sulfoxide (DMSO) were added to the wells and serially diluted twofold. The final concentration of DMSO did not exceed 1% (v/v). Cycloheximide was used as a positive control for antifungal activity, while oxytetracycline served as a positive control for antibacterial activity. A solution containing 1% DMSO was used as the negative control. The microtiter plates were incubated for 1–3 days, and MIC values were determined by visual inspection as the lowest concentration showing complete growth inhibition of visible growth (Kim et al., 2024). All assays were performed in triplicate and repeated independently twice.

Mycelial growth inhibition assay

To evaluate the effect of compound 1 on mycelial growth, mycelial discs (5 mm in diameter) of B. cinerea, Colletotrichum coccodes, and P. infestans were inoculated onto agar media containing the indicated concentrations of compound 1. PDA medium was used for B. cinerea and C. coccodes, while V8 agar (200 mL of V8 juice, 3 g of CaCO3, 15 g of agar, and 1 L of distilled water) was used for P. infestans. Radial mycelial growth was measured at 7 days post-inoculation (dpi). Agar plates containing 1% DMSO and cycloheximide (10 μg/mL) served as negative and positive controls, respectively. Inhibition rate (%) was calculated using the following equation: Inhibition rate (%) = 100 × [1 – B/A], where A is the mycelium radial growth of control plates, and B is the mycelium radial growth of treated plates (Park et al., 2025). All experiments were conducted in triplicate and independently repeated twice.

Disease control efficacy assay

To evaluate the disease control efficacy of the culture filtrate, extracts, and purified compounds, six plant diseases caused by fungal and oomycete pathogens were used; rice blast (RCB; caused by Magnaporthe oryzae), tomato gray mold (TGM; caused by B. cinerea), tomato late blight (TLB; caused by P. infestans), wheat leaf rust (WLR; caused by Puccinia triticina), barley powdery mildew (BPM; caused by Blumeria graminis f. sp. hordei), and pepper anthracnose (PAN; caused by C. coccodes). For treatments, the culture filtrate containing 0.025% (v/v) Tween 20 was applied to the plants by spraying. The solvent extracts and the isolated compounds were initially dissolved in DMSO–MeOH (1:1, v/v) and then diluted with 0.025% (v/v) Tween 20 solution to the desired final concentrations. Chemical fungicides (blasticidin-S, fludioxonil, dimethomorph, flusilazole, and dithianon) were used as positive controls, whereas 1% (v/v) DMSO–MeOH solution served as the negative control. Rice (Oryza sativa L., cv. Chucheong), tomato (Solanum lycopersicum cv. Seokwang), wheat (Triticum aestivum cv. Geumgang), barley (Hordeum sativum cv. Hanyoung), and pepper (Capsicum annuum cv. Misocheonguk) plants were grown in a greenhouse at 25 ± 5°C for 1 to 4 weeks and used as host plants. After treatment, plants were maintained for 24 h to assess phytotoxicity, followed by inoculation with the respective fungal pathogens and incubation as previously described (Ngo et al., 2020). Disease severity was assessed based on the percentage of leaf lesion area at 3 to 7 dpi. Disease control efficacy (%) was calculated as follows: control efficacy (%) = 100 × [1 – B/A], where A represents the mean lesion area (%) on the leaves of control plants, and B represents the mean lesion area (%) on the leaves of treated plants. All experiments were performed in triplicate and independently repeated twice.

Results

In vitro and in vivo antifungal activities of CF-E and ME-E extracts

In the ongoing exploration of antifungal agents derived from marine fungi, the culture filtrate of A. udagawae SFC20170619-M03 exhibited significant disease control efficacy against plant diseases caused by fungi, including tomato late blight, wheat leaf rust, and pepper anthracnose (Supplementary Table 2). To identify the active components responsible for this activity, the culture filtrate and mycelial extracts of A. udagawae SFC20170619-M03 were successively partitioned with equal volumes of EtOAc and BuOH, yielding CF-E, CF-B, CF-W, ME-E, ME-B, and ME-W extracts (Supplementary Fig. 1). Evaluation of these extracts for in vitro antifungal activity revealed that CF-E and ME-E extracts exhibited broad-spectrum antifungal activity, with MICs ranging from 16 to 250 μg/mL (Supplementary Table 3). However, the other extracts exhibited no detectable in vitro antifungal activity at concentrations up to 500 μg/mL (Supplementary Table 3). In the in vivo antifungal assay, the ME-E extract showed strong disease control efficacy against rice blast, tomato late blight, and pepper anthracnose, with control values of 95%, 94%, and 93%, respectively, at a concentration of 1,000 μg/mL, whereas CF-E extract exhibited weak disease control efficacies against rice blast, tomato gray mold, and pepper anthracnose at the same concentrations (Supplementary Table 2). Similar to in vitro antifungal activity, the CF-B, CF-W, ME-B, and ME-W extracts exhibited no detectable disease control efficacy at concentrations up to 1,000 μg/mL. Taken together, we selected the CF-E and ME-E extracts for further isolation and characterization of active secondary metabolites.

Structural elucidation of isolated compounds from A. udagawae SFC20170619-M03

The CF-E and ME-E extracts were subjected to successive chromatographic separations, resulting in the isolation of eleven compounds (2 and 7–16) from the CF-E extract and five compounds (1 and 3–6) from the ME-E extract (Supplementary Figs. 1 and 2). The structures of the isolated compounds were elucidated based on spectroscopic analyses, including NMR and MS data, in combination with comparison to literature data. The isolated compounds were identified as MS-347a (1) (Nakanishi et al., 1993), sydowinin B (2) (Hamasaki et al., 1975), sydowinin A (3) (Hamasaki et al., 1975), pinselin (4) (Law et al., 1979), 4-hydroxyvertixanthone (5) (Chen et al., 2024), methyl-8-hydroxy-6-methyl-9-oxo-9H-xanthene-1-carboxylate (6) (Shao et al., 2008), AGI-B4 (7) (Kim et al., 2002), engyodontiumone H (8) (Yao et al., 2014), arthone A (9) (Bao et al., 2018), fumigatin (10) (Packter and Glover, 1965), spinulosin (11) (Anslow and Raistrick, 1938), asperfumtone B (12) (Wu et al., 2024), pseurotin A (13) (Ishikawa et al., 2009), pseurotin F1 (14) (Ishikawa et al., 2009), pseurotin F2 (15) (Ishikawa et al., 2009), and fumagillin (16) (Guruceaga et al., 2019) (Fig. 1, Supplementary Figs. 1 and 3–18, and Supplementary Table 4).

Fig. 1.

Fig. 1

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Chemical structure of compounds 1–16 isolated from the fungus Aspergillus udagawae SFC20170619-M03.

In vitro antimicrobial activity of the identified compounds against plant pathogens

The isolated compounds (1–16) were evaluated for their antifungal activity against eight plant pathogenic fungi using a microdilution-based in vitro assay. As summarized in Table 1, the oomycete P. infestans was the most sensitive among the tested fungal pathogens, exhibiting MIC values ranging from 3.2 to 400 μg/mL. Compounds 6, 9, 11, and 13–15 did not exhibit inhibitory activity against P. infestans at concentrations up to 400 μg/mL. Among the xanthone derivatives (1–9), three dihydroxanthenone compounds (1, 7, and 8) exhibited strong antifungal activity against P. infestans, with MIC values of 3.2, 6.3, and 6.3 μg/mL, respectively, comparable to those of the xanthone-8-carboxylate derivatives (2–5). Notably, compound 1 exhibited potent and broad-spectrum antifungal activity against M. oryzae, A. brassicicola, F. oxysporum, C. coccodes, and C. destructans, with MIC values of 6.3, 12.5, 25, 25, and 100 μg/mL, respectively. In contrast, compounds 7 and 8 showed weak or no antifungal activity against these pathogenic fungi. The ubiquinone derivatives (10–12) showed limited antifungal activity, with MIC values ranging from 12.5 to 400 μg/mL. Compound 16 showed antifungal activity against P. infestans, M. oryzae, A. brassicicola, and C. coccodes, with MIC values of 6.3, 200, 400, and 400 μg/mL, respectively, but was inactive against the remaining fungal pathogens. Compounds 13–15 showed no detectable antifungal activity against any of the tested fungi at concentrations up to 400 μg/mL.

Table 1.

In vitro antifungal activity of compounds 1–16 against plant pathogenic fungi

Compound Minimum inhibitory concentration (MIC; μg/mL)
Ab Bc Clc Coc Cd Fo Mo Pi
1 12.5 - - 25 100 25 6.3 3.2
2 -* - - - - - - 400
3 - - - - - - - 100
4 - - - - - 200 - 100
5 - - - - - - - 50
6 - - - - - - - -
7 400 - - - - - 200 6.3
8 400 - - - - - 200 6.3
9 - - - - - - - -
10 400 - 400 400 400 100 200 50
11 - - - - - - - -
12 400 - - - - 200 200 12.5
13 - - - - - - - -
14 - - - - - - - -
15 - - - - - - - -
16 400 - - 400 - - 200 6.3
Cycloheximide 6.3 50 12.5 12.5 12.5 6.3 6.3 0.8
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Ab, Alternaria brassicicola; Bc, Botrytis cinerea; Clc, Cladosporium cucumerinum; Coc, Colletotrichum coccodes; Cd, Cylindrocarpon destructans; Fo, Fusarium oxysporum; Mo, Magnaporthe oryzae; Pi, Phytophthora infestans.

*

Indicates MIC >400 μg/mL.

In addition to antifungal activity, the isolated compounds were assessed for antibacterial activity against twelve plant pathogenic bacteria. As shown in Table 2, among the xanthone derivatives (1–9), compound 1 exclusively exhibited antibacterial activity against Acidovorax avenae subsp. cattleyae, Acidovorax citrulli, and Agrobacterium tumefaciens, with MIC values of 25, 12.5, and 12.5 μg/mL, respectively. The ubiquinone derivatives (10–12) showed broad but moderate antibacterial activity, with MIC values ranging from 25 to 400 μg/mL. In contrast, compounds 13–16 did not exhibit antibacterial activity against any of the tested bacteria at concentrations up to 400 μg/mL.

Table 2.

In vitro antibacterial activity of compounds 1–16 against plant pathogenic bacteria

Compound Minimum inhibitory concentration (MIC; μg/mL)
Aa Ac At Bg Cm Dc Ea Pc Ps Rs Xa Xc
1 25 12.5 12.5 - - - - - - - - -
2 -* - - - - - - - - - - -
3 - - - - - - - - - - - -
4 - - - - - - - - - - - -
5 - - - - - - - - - - - -
6 - - - - - - - - - - - -
7 - - - - - - - - - - - -
8 - - - - - - - - - - - -
9 - - - - - - - - - - - -
10 50 50 100 200 100 100 200 100 100 50 50 50
11 400 - - - 400 - - - - 200 200 200
12 400 400 - - - 200 50 200 400 200 400 400
13 - - - - - - - - - - - -
14 - - - - - - - - - - - -
15 - - - - - - - - - - - -
16 - - - - - - - - - - - -
Oxytetracycline 50 12.5 25 3.2 0.8 0.4 6.3 6.3 12.5 0.8 1.6 1.6
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Aa, Acidovorax avenae subsp. cattleyae; Ac, Acidovorax citrulli; At, Agrobacterium tumefaciens; Bg, Burkholderia glumae; Cm, Clavibacter michiganensis subsp. michiganensis; Dc, Dickeya chrysanthemi; Ea, Erwinia amylovora; Pc, Pectobacterium carotovorum subsp. carotovorum; Ps, Pseudomonas syringae pv. actinidiae; Rs, Ralstonia solanacearum; Xa, Xanthomonas arboricola pv. pruni; Xc, Xanthomonas campestris pv. campestris.

*

Indicates MIC >400 μg/mL.

Effect of MS-347a (1) on the mycelial growth

Considering that MS-347a (1) exhibited the strongest antifungal activity among the identified compounds in the conidial suspension assay, its inhibitory effects on the mycelial growth of B. cinerea, C. coccodes, and P. infestans were further evaluated on agar media supplemented with different concentrations of the compound. MS-347a (1) inhibited the mycelial growth of B. cinerea by 23%, 84%, and 100% at concentrations of 25, 50, and 100 μg/mL, respectively, compared with the untreated control, despite showing no antifungal activity against the conidial suspension of B. cinerea at concentrations up to 400 μg/mL (Fig. 2, Table 1). These results suggest that MS-347a (1) exerts greater inhibitory activity against the mycelial growth than against conidial germination in B. cinerea. Similarly, the mycelial growth of C. coccodes was reduced by 0%, 63%, and 83% at the same concentrations (Fig. 2). In contrast, P. infestans was more sensitive to MS-347a (1), exhibiting growth inhibition of 26%, 69%, and 98% at lower concentrations of 1.6, 3.2, and 6.4 μg/mL, respectively (Fig. 2). The EC50 values for B. cinerea, C. coccodes, and P. infestans were 35.3 ± 0.7, 51.0 ± 0.1, and 2.4 ± 0.1 μg/mL, respectively, further demonstrating that MS-347a (1) exhibited the strongest inhibitory activity in vitro against the mycelial growth of P. infestans.

Fig. 2.

Fig. 2

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Inhibitory effects of MS-347a (1) on the mycelial growth of (A) Botrytis cinerea, (B) Colletotrichum coccodes, and (C) Phytophthora infestans. Plates containing 1% DMSO were used as negative controls (NC), whereas plates containing cycloheximide (10 μg/mL) were used as positive controls (PC). Colony diameters were measured and photographs were taken at 7 days post-inoculation.

Compounds 1, 7, 10, and 16 effectively controlled fungal plant diseases

Based on in vitro antifungal activities and the availability of sufficient quantities for bioassays (Table 1, Supplementary Table 4), MS-347a (1), AGI-B4 (7), fumigatin (10), and fumagillin (16) were selected for further evaluation of their in vivo disease control efficacy against six fungal plant diseases. When the compounds were applied to plants prior to pathogen inoculation, MS-347a (1) exhibited promising disease control efficacy, showing over 88% of the control values against tomato gray mold and tomato late blight at the tested concentrations compared with the non-treatment control (Fig. 3, Supplementary Table 5). In addition, MS-347a (1) exhibited moderate disease control efficacy against rice blast and pepper anthracnose, with control values of 56% and 70%, respectively, at a concentration of 125 μg/mL (Fig. 3, Supplementary Table 5). However, MS-347a (1) exhibited weak or no disease control activity against wheat leaf rust and barley powdery mildew (Fig. 3, Supplementary Table 5). AGI-B4 (7) and engyodontiumone H (8) exhibited strong and selective in vitro anti-oomycete activity against P. infestans, comparable to that of MS-347a (1) (Table 1). Based on these results, AGI-B4 (7) was selected for further in vivo evaluation against tomato late blight. When applied to tomato plants prior to pathogen inoculation, AGI-B4 (7) exhibited dose-dependent disease control, with control efficacies of 25%, 38%, and 91% at concentrations of 125, 250, and 500 μg/mL, respectively, relative to the non-treated control (Fig. 4, Supplementary Table 5). Among the benzoquinone derivatives, fumigatin (10) showed moderate disease control efficacy against tomato gray mold, with control values of 55%, 65%, and 70% at concentrations of 250, 500, and 1,000 μg/mL, respectively, whereas the other plant diseases were not effectively suppressed (Fig. 5, Supplementary Table 5). The polyene compound fumagillin (16) exhibited moderate disease control efficacy against rice blast and pepper anthracnose. The disease control values against rice blast were 25%, 56%, and 63% at concentrations of 125, 250, and 500 μg/mL, respectively, whereas those against pepper anthracnose were 35%, 75%, and 80% at the same concentrations (Fig. 5, Supplementary Table 5).

Fig. 3.

Fig. 3

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Effect of MS-347a (1) on the development of plant diseases. (A) Disease control efficacy of MS-347a (1) against various plant diseases. RCB, rice blast; TGM, tomato gray mold; TLB, tomato late blight; WLR, wheat leaf rust; BPM, barley powdery mildew; and PAN, pepper anthracnose. Bars represent the mean ± standard deviation of two independent experiments with three replicates. nd, not detected. (B–D) Representative images of plants treated with MS-347a (1) in the disease control efficacy assay. NC, treatment with Tween 20 solution containing 1% (v/v) DMSO–MeOH solution as the negative control; a–c, treatment with MS-347a (1) at concentrations of 62.5, 125, and 250 μg/mL, respectively; PC, treatment with chemical fungicide as positive controls: blasticidin S (50 μg/mL) for RCB, fludioxonil (50 μg/mL) for TGM, dimethomorph (10 μg/mL) for TLB, flusilazole (10 μg/mL) for WLR, benomyl (100 μg/mL) for BPM, and dithianon (50 μg/mL) for PAN.

Fig. 4.

Fig. 4

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Effect of AGI-B4 (7) on the development of tomato late blight. The left panel shows disease control efficacy against tomato late blight, and the right panel presents representative images of the tomato plants treated with AGI-B4 (7). NC, treatment with Tween 20 solution containing 1% (v/v) DMSO–MeOH solution as the negative control; PC, treatment with dimethomorph (10 μg/mL) as a positive control. Bar graphs represent the mean ± standard deviation from two independent experiments with three replicates.

Fig. 5.

Fig. 5

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Effect of fumigatin (10) and fumagillin (16) on the development of plant diseases. (A) Disease control efficacy of fumigatin (10) against tomato gray mold (TGM) and pepper anthracnose (PAN). The right panel shows representative images of the tomato plants treated with fumigatin (10). (B) Disease control efficacy of fumagillin (16) against rice blast (RCB) and pepper anthracnose (PAN). The right panel shows representative images of pepper plants treated with fumagillin (16). NC, treatment with Tween 20 solution containing 1% (v/v) DMSO–MeOH solution as the negative control; PC, treatment with chemical fungicide as positive controls: fludioxonil (50 μg/mL) for TGM, dithianon (50 μg/mL) for PAN, and blasticidin S (50 μg/mL) for RCB. All bar graphs represent the mean ± standard deviation from two independent experiments with three replicates.

Discussion

In this study, sixteen secondary metabolites were identified from the marine-derived fungus A. udagawae SFC20170619-M03, and MS-347a (1) was identified as the principal antimicrobial metabolite based on its production yield and biological activity. Among the isolated compounds, xanthones, benzoquinones, and fumagillin derivatives exhibited distinct antimicrobial profiles, highlighting the chemical and biological diversity of metabolites produced by this strain.

MS-347a (1) is known as an irreversible inhibitor of smooth muscle myosin light chain kinase through covalent modification mediated by its epoxide group (Nakanishi et al., 1993). Consistent with its previously reported broad biological activities (Hamasaki et al., 1975; Honma et al., 2024), MS-347a (1) exhibited broad-spectrum antimicrobial activity against plant pathogenic fungi and bacteria, with MIC values ranging from 3 to 100 μg/mL. In addition, propidium iodide staining assay demonstrated disruption of membrane integrity in both B. cinerea and P. infestans, suggesting that membrane damage may contribute to its antimicrobial activity. (Supplementary Figs. 19, 20). Comparison of the isolated xanthones further indicated that the epoxide moiety is a key structural feature responsible for the broad-spectrum activity of MS-347a (1). Xanthones (2–9), which lack this epoxide moiety, generally exhibited weaker or no antimicrobial activity. This observation is consistent with previous reports demonstrating that the epoxide groups enhances the biological activity of structurally diverse natural products through their ability to form covalent adducts with nucleophilic residues in biological macromolecules (Kóňa, 2008; Lidert et al., 1997; Torres et al., 1998). Although the molecular targets responsible for the antimicrobial activity of MS-347a (1) remain unknown, the epoxide group appears to play a central role in its biological activity.

In contrast to the broad-spectrum activity of MS-347a (1), the non-epoxidized xanthones AGI-B4 (7) and engyodontiumone H (8) exhibited potent and selective activity against P. infestans, indicating that removal of the epoxide group markedly alters the biological activity profile. To our knowledge, this is the first report demonstrating the anti-oomycete activity of AGI-B4 (7) and engyodontiumone H (8), both showing MIC values of 6.3 μg/mL. Furthermore, AGI-B4 (7) significantly suppressed tomato late blight under greenhouse conditions, supporting its potential as a lead compound for controlling Phytophthora diseases. Because AGI-B4 (7) and engyodontiumone H (8) were co-isolated with MS-347a (1) and share closely related xanthone skeletons, they may represent biosynthetic intermediates or shunt metabolites in the MS-347a (1) biosynthetic pathway, although this hypothesis requires experimental validation.

The isolated benzoquinones (10–12) exhibited moderate antimicrobial activity, with MIC values ranging from 12.5 to 400 μg/mL. Quinone compounds are well known to possess diverse biological activities through redox cycling and reactive oxygen species generation (Gueven et al., 2015; Sarewicz and Osyczka, 2015). While fumigatin (10), spinulosin (11), and asperfumtone B (12) have previously been reported to possess antibacterial, nematicidal, or antifungal activities (Hayashi et al., 2007; Oxford and Raistrick, 1942; Waksman and Geiger, 1944; Wu et al., 2024), the present study extends their antimicrobial spectrum to several plant pathogens and further supports the benzoquinone scaffold as a promising source of antimicrobial agents.

Fumagillin (16), originally isolated from A. fumigatus, exhibits potent activity against several eukaryotic parasites, including Entamoeba histolytica, Encephalitozoon cuniculi, and Nosema apis, as well as against Staphylococcus aureus, and also demonstrates anticancer properties (Guruceaga et al., 2019; Van Den Heever et al., 2014). Its principal mechanism of action involves the irreversible inhibition of methionine aminopeptidase type 2 (MetAP-2) through covalent modification of the catalytic histidine residue (His231) in the enzyme (Zhang et al., 2006). The spiro-epoxide group on the cyclohexane core is critical for this activity, and opening or modification of the epoxide markedly reduces MetAP-2 inhibition (Van Den Heever et al., 2014). However, the ability of fumagillin (16) to inhibit mammalian MetAP-2 raises substantial toxicity concerns and limits its broader agricultural and therapeutic applications (Guruceaga et al., 2019; Van Den Heever et al., 2014). Its practical use is further constrained by its sensitivity to heat and UV irradiation (Van Den Heever et al., 2014). Although fumagillin (16) possesses biologically relevant activity, its potential use as a crop-protection agent would require careful assessment of its stability, residue persistence, and toxicity.

In conclusion, this study demonstrated that A. udagawae SFC20170619-M03 produces structurally diverse secondary metabolites with distinct antimicrobial activities. MS-347a (1) was identified as the major antimicrobial metabolite, and comparison of structurally related xanthones highlighted the importance of the epoxide moiety for broad-spectrum antimicrobial activity. In contrast, the non-epoxidized xanthones AGI-B4 (7) and engyodontiumone H (8) exhibited potent and selective anti-oomycete activity, with AGI-B4 (7) also providing effective control of tomato late blight in vivo. These findings identify MS-347a (1), AGI-B4 (7), and engyodontiumone H (8) as promising lead compounds for the development of natural crop-protection agents. Further studies should focus on elucidating their molecular targets, biosynthetic pathways, field efficacy, and environmental safety.

Footnotes

Conflicts of Interest

No potential conflict of interest relevant to this article was reported.

Acknowledgments

This study was carried out with the support of Cooperative Research Program for Agriculture Science and Technology Development funded by Rural Development Administration (Project No. RS-2024-00399621), Korea Institute of Planning and Evaluation for Technology in Food, Agriculture, Forestry, and Fisheries (IPET) through Advanced Biotechnology-based Green Biomaterial Industrialization Technology Development Project, funded by the Ministry of Agriculture, Food, and Rural Affairs (MAFRA) (Project No. RS-2026-25526672), and Korea Research Institute of Chemical Technology (KRICT) intramural funding (Project No. KK2632-20).

Electronic Supplementary Material

Supplementary materials are available at The Plant Pathology Journal website (http://www.ppjonline.org/).

References

  1. Amaike S., Keller N. P. Aspergillus flavus . Annu. Rev. Phytopathol. 2011;49:107–133. doi: 10.1146/annurev-phyto-072910-095221. [DOI] [PubMed] [Google Scholar]
  2. Anslow W. K., Raistrick H. Studies in the biochemistry of micro-organisms: Fumigatin (3-hydroxy-4-methoxy-2:5-toluquinone), and spinulosin (3:6-dihydroxy-4-methoxy-2:5-toluquinone), metabolic products respectively of Aspergillus fumigatus Fresenius and Penicillium spinulosum Thom. Biochem. J. 1938;32:687–696. doi: 10.1042/bj0320687. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Atallah O., Yassin S. Aspergillus spp. eliminate Sclerotinia sclerotiorum by imbalancing the ambient oxalic acid concentration and parasitizing its sclerotia. Environ. Microbiol. 2020;22:5265–5279. doi: 10.1111/1462-2920.15213. [DOI] [PubMed] [Google Scholar]
  4. Bao J., He F., Yu J. H., Zhai H., Cheng Z. Q., Jiang C. S., Zhang Y., Zhang Y., Zhang X., Chen G., Zhang H. New chromones from a marine-derived fungus, Arthrinium sp., and their biological activity. Molecules. 2018;23:1982. doi: 10.3390/molecules23081982. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Chen H. W., Wu X. Y., Zhao Z. Y., Huang Z. Q., Lei X. S., Yang G. X., Li J., Xiong J., Hu J. F. Terricoxanthones A–E, unprecedented dihydropyran-containing dimeric xanthones from the endophytic fungus Neurospora terricola HDF-Br-2 associated with the vulnerable conifer Pseudotsuga gaussenii. Phytochemistry. 2024;219:113963. doi: 10.1016/j.phytochem.2023.113963. [DOI] [PubMed] [Google Scholar]
  6. Copping L. G., Duke S. O. Natural products that have been used commercially as crop protection agents. Pest Manag. Sci. 2007;63:524–554. doi: 10.1002/ps.1378. [DOI] [PubMed] [Google Scholar]
  7. Ehrlich K. C. Non-aflatoxigenic Aspergillus flavus to prevent aflatoxin contamination in crops: Advantages and limitations. Front. Microbiol. 2014;5:50. doi: 10.3389/fmicb.2014.00050. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. El-Hawary S. S., Moawad A. S., Bahr H. S., Abdelmohsen U. R., Mohammed R. Natural product diversity from the endophytic fungi of the genus Aspergillus. RSC Adv. 2020;10:22058–22079. doi: 10.1039/d0ra04290k. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Fisher M. C., Hawkins N. J., Sanglard D., Gurr S. J. Worldwide emergence of resistance to antifungal drugs challenges human health and food security. Science. 2018;360:739–742. doi: 10.1126/science.aap7999. [DOI] [PubMed] [Google Scholar]
  10. Gai Y., Wang H. Plant disease: A growing threat to global food security. Agronomy. 2024;14:1615. [Google Scholar]
  11. Gao T., Hao F., Yang D., Bie Z., Li G. Oxalic acid produced by Aspergillus niger Y-1 is effective for suppression of bacterial fruit blotch of watermelon seedlings. Biol. Control. 2017;112:28–33. [Google Scholar]
  12. Gueven N., Woolley K., Smith J. Border between natural product and drug: Comparison of the related benzoquinones idebenone and coenzyme Q10 . Redox Biol. 2015;4:289–295. doi: 10.1016/j.redox.2015.01.009. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Guruceaga X., Perez-Cuesta U., De Cerio A. A. D., Gonzalez O., Alonso R. M., Hernando F. L., Ramirez-Garcia A., Rementeria A. Fumagillin, a mycotoxin of Aspergillus fumigatus: Biosynthesis, biological activities, detection, and applications. Toxins. 2019;12:7. doi: 10.3390/toxins12010007. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Hamasaki T., Sato Y., Hatsuda Y. Structure of sydowinin A, sydowinin B, and sydowinol, metabolites from Aspergillus sydowi. Agr. Biol. Chem. 1975;39:2341–2345. [Google Scholar]
  15. Hayashi A., Fujioka S., Nukina M., Kawano T., Shimada A., Kimura Y. Fumiquinones A and B, nematicidal quinones produced by Aspergillus fumigatus. Biosci. Biotech. Biochem. 2007;71:1697–1702. doi: 10.1271/bbb.70110. [DOI] [PubMed] [Google Scholar]
  16. Honma S., Kimishima A., Kimishima A., Honsho M., Kojima H., Tokiwa T., Nishitomi A., Kato S., Kondo N., Araki Y., Takahashi T., Chinen T., Usui T., Fuji S. I., Ito K., Asami Y. Re-discovery of MS-347a as a fungicide candidate through a new drug discovery platform with a multidrug-sensitive Saccharomyces cerevisiae screening system and the introduction of a global secondary metabolism regulator, laeA gene. Biosci. Biotech. Biochem. 2024;88:824–829. doi: 10.1093/bbb/zbae050. [DOI] [PubMed] [Google Scholar]
  17. Ishikawa M., Ninomiya T., Akabane H., Kushida N., Tsujiuchi G., Ohyama M., Gomi S., Shito K., Murata T. Pseurotin A and its analogues as inhibitors of immunoglobuline E production. Bioorg. Med. Chem. Lett. 2009;19:1457–1460. doi: 10.1016/j.bmcl.2009.01.029. [DOI] [PubMed] [Google Scholar]
  18. Jang J. Y., Choi Y. H., Shin T. S., Kim T. H., Shin K. S., Park H. W., Kim Y. H., Kim H., Choi G. J., Jang K. S., Cha B., Kim I. S., Myung E. J., Kim J. C. Biological control of Meloidogyne incognita by Aspergillus niger F22 producing oxalic acid. PLoS One. 2016;11:e0156230. doi: 10.1371/journal.pone.0156230. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Kim B., Kim Y. S., Han J. W., Yu J. S., Kim T. H., Shin T. S., Choi G. J., Kim H. Biocontrol potential of Bevibacillus brevis HK544 for fungal plant diseases. Biol. Control. 2024;198:105629. [Google Scholar]
  20. Kim H. S., Park I. Y., Park Y. J., Lee J. H., Hong Y. S., Lee J. J. A novel dihydroxanthenone, AGI-B4 with inhibition of VEGF-induced endothelial cell growth. J. Antibiot. 2002;55:669–672. doi: 10.7164/antibiotics.55.669. [DOI] [PubMed] [Google Scholar]
  21. Kóňa J. Theoretical study on the mechanism of a ring-opening reaction of oxirane by the active-site aspartic dyad of HIV-1 protease. Org. Biomol. Chem. 2008;6:359–365. doi: 10.1039/b715828a. [DOI] [PubMed] [Google Scholar]
  22. Lavkor I., Ay T., Sobucovali S., Var I., Saghrouchni H., Salamatullah A. M., Mekonnen A. B. Non-aflatoxigenic Aspergillus flavus: A promising biological control agent against aflatoxin contamination of corn. ACS Omega. 2023;8:16779–16788. doi: 10.1021/acsomega.3c00303. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Law K.-K., Chan T.-L., Tam S. W., Ahatin N. T. Synthesis of pinselic acid and pinselin. J. Org. Chem. 1979;44:4452–4453. [Google Scholar]
  24. Li X. J., Zhang Q., Zhang A. L., Gao J. M. Metabolites from Aspergillus fumigatus, an endophytic fungus associated with Melia azedarach, and their antifungal, antifeedant, and toxic activities. J. Agric. Food Chem. 2012;60:3424–3431. doi: 10.1021/jf300146n. [DOI] [PubMed] [Google Scholar]
  25. Lidert Z., Young D. H., Bowers-Daines M. M., Sherba S. E., Mehta R. J., Lange B. C., Swithenbank C., Kiyokawa H., Johnson M. G., Morris-Natschke S. L., Lee K. H. 1,4-Bis-(2,3-epoxypropylamino)-9,10-anthracenedione and related compounds as potent antifungal and antimicrobial agents. Bioorg. Med. Chem. Lett. 1997;7:3153–3158. [Google Scholar]
  26. Liu K., Zheng Y., Miao C., Xiong Z., Xu L., Guan H., Yang Y., Zhao L. The antifungal metabolites obtained from the rhizospheric Aspergillus sp. YIM PH30001 against pathogenic fungi of Panax notoginseng. Nat. Prod. Res. 2014;28:2334–2337. doi: 10.1080/14786419.2014.935941. [DOI] [PubMed] [Google Scholar]
  27. Nakanishi S., Ando K., Kawamoto I., Matsuda Y. MS-347a, a new inhibitor of myosin light chain kinase from Aspergillus sp. KY52178. J. Antibiot. 1993;46:1775–1781. doi: 10.7164/antibiotics.46.1775. [DOI] [PubMed] [Google Scholar]
  28. Ngo M. T., Han J. W., Nguyen M. N., Dang Q. L., Kim H., Choi G. J. Antifungal properties of natural products from Pterocarya tonkinensis against phytopathogenic fungi. Pest Manag. Sci. 2020;77:1864–1872. [Google Scholar]
  29. Nguyen M. V., Han J. W., Kim H., Choi G. J. Phenyl ethers from the marine-derived fungus Aspergillus tabacinus and their antimicrobial activity against plant pathogenic fungi and bacteria. ACS Omega. 2022;7:33273–33279. doi: 10.1021/acsomega.2c03859. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Oxford A. E., Raistrick H. Anti-bacterial substances from moulds. IV. Spinulosin and fumigatin. Chem. Indust. 1942;61:128–129. [Google Scholar]
  31. Packter N. M., Glover J. Biosynthesis of [14C]fumigatin in Aspergillus fumigatus, fresenius. Biochim. Biophys. Acta-Gen. Subj. 1965;100:50–56. doi: 10.1016/0304-4165(65)90426-5. [DOI] [PubMed] [Google Scholar]
  32. Park J. H., Han J. W., Kim B., Park S. U., Choi G. J., Kim H. Suppression of rice blast and tomato late blight by Paraboeremia adianticola producing vulculic acid. Pest Manag. Sci. 2025;81:5052–5061. doi: 10.1002/ps.8859. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Rodrigo S., García-Latorre C., Santamaria O. Metabolites produced by fungi against fungal phytopathogens: Review, implementation and perspectives. Plants. 2022;11:81. doi: 10.3390/plants11010081. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Sarewicz M., Osyczka A. Electronic connection between the quinone and cytochrome c redox pools and its role in regulation of mitochondrial electron transport and redox signaling. Physiol. Rev. 2015;95:219–243. doi: 10.1152/physrev.00006.2014. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Shao C., Wang C., Wei M., Gu Y., Xia X., She Z., Lin Y. Structure elucidation of two new xanthone derivatives from the marine fungus Penicillium sp. (ZZF 32#) from the South China Sea. Magn. Reson. Chem. 2008;46:1066–1069. doi: 10.1002/mrc.2293. [DOI] [PubMed] [Google Scholar]
  36. Torres M., Balcells M., Sala N., Sanchis V., Canela R. Bactericidal and fungicidal activity of Aspergillus ochraceus metabolites and some derivatives. Pestic. Sci. 1998;53:9–14. [Google Scholar]
  37. Vadlapudi V., Borah N., Yellusani K. R., Gade S., Reddy P., Rajamanikyam M., Vempati L. N. S., Gubbala S. P., Chopra P., Upadhyayula S. M., Amanchy R. Aspergillus secondary metabolite database, a resource to understand the secondary metabolome of Aspergillus genus. Sci. Rep. 2017;7:7325. doi: 10.1038/s41598-017-07436-w. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. Van Den Heever J. P., Thompson T. S., Curtis J. M., Ibrahim A., Pernal S. F. Fumagillin: An overview of recent scientific advances and their significance for apiculture. J. Agric. Food Chem. 2014;62:2728–2737. doi: 10.1021/jf4055374. [DOI] [PubMed] [Google Scholar]
  39. Waard M. A., Georgopoulos S. G., Hollomon D. W., Ishii H., Leroux P., Ragsdale N. N., Schwinn F. J. Chemical control of plant diseases: Problems and prospects. Annu. Rev. Phytopathol. 1993;31:403–421. [Google Scholar]
  40. Waksman S. A., Geiger W. B. The nature of the antibiotic substances produced by Aspergillus fumigatus. J. Bacteriol. 1944;47:391–397. doi: 10.1128/jb.47.4.391-397.1944. [DOI] [PMC free article] [PubMed] [Google Scholar]
  41. Wang S., Wang Y., Shi X., Herrera-Balandrano D. D., Chen X., Liu F., Laborda P. Application and antagonistic mechanisms of atoxigenic Aspergillus strains for the management of fungal plant diseases. Appl. Environ. Microbiol. 2024;90:e0108524. doi: 10.1128/aem.01085-24. [DOI] [PMC free article] [PubMed] [Google Scholar]
  42. Wu Y. M., Yang X. Q., Yang YBin Cai L., He F. F., Ding Z. T. The antifungal metabolites from coculture of Aspergillus fumigatus and Alternaria alternata associated with Coffea arabica. Nat. Prod. Res. 2024;38:753–758. doi: 10.1080/14786419.2023.2196722. [DOI] [PubMed] [Google Scholar]
  43. Xiao J., Zhang Q., Gao Y. Q., Shi X. W., Gao J. M. Antifungal and antibacterial metabolites from an endophytic Aspergillus sp. associated with Melia azedarach. Nat. Prod. Res. 2014;28:1388–1392. doi: 10.1080/14786419.2014.904308. [DOI] [PubMed] [Google Scholar]
  44. Yao Q., Wang J., Zhang X., Nong X., Xu X., Qi S. Cytotoxic polyketides from the deep-sea-derived fungus Engyodontium album DFFSCS021. Mar. Drugs. 2014;12:5902–5915. doi: 10.3390/md12125902. [DOI] [PMC free article] [PubMed] [Google Scholar]
  45. Yin Y., Miao J., Shao W., Liu X., Zhao Y., Ma Z. Fungicide resistance: Progress in understanding mechanism, monitoring, and management. Phytopathology. 2023;113:707–718. doi: 10.1094/PHYTO-10-22-0370-KD. [DOI] [PubMed] [Google Scholar]
  46. Zhang Y., Yeh J. R., Mara A., Ju R., Hines J. F., Cirone P., Griesbach H. L., Schneider I., Slusarski D. C., Holley S. A., Crews C. M. A chemical and genetic approach to the mode of action of fumagillin. Chem. Biol. 2006;13:1001–1009. doi: 10.1016/j.chembiol.2006.07.010. [DOI] [PMC free article] [PubMed] [Google Scholar]
  47. Zhou W., Li M., Achal V. A comprehensive review on environmental and human health impacts of chemical pesticide usage. Emerg. Contam. 2025;11:100410. [Google Scholar]

Associated Data

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Supplementary Materials

PPJ-OA-08-2026-0108-Supplementary-Fig-1.pdf (531.6KB, pdf)
PPJ-OA-08-2026-0108-Supplementary-Fig-2,3.pdf (860.2KB, pdf)
PPJ-OA-08-2026-0108-Supplementary-Fig-4,5.pdf (197.8KB, pdf)
PPJ-OA-08-2026-0108-Supplementary-Fig-6,7.pdf (248KB, pdf)
PPJ-OA-08-2026-0108-Supplementary-Fig-8,9.pdf (310.2KB, pdf)
PPJ-OA-08-2026-0108-Supplementary-Fig-10,11.pdf (293.4KB, pdf)
PPJ-OA-08-2026-0108-Supplementary-Fig-12,13.pdf (356.9KB, pdf)
PPJ-OA-08-2026-0108-Supplementary-Fig-14,15.pdf (252KB, pdf)
PPJ-OA-08-2026-0108-Supplementary-Fig-16,17.pdf (265.2KB, pdf)
PPJ-OA-08-2026-0108-Supplementary-Fig-18,19.pdf (444.5KB, pdf)
PPJ-OA-08-2026-0108-Supplementary-Fig-20.pdf (292.2KB, pdf)
PPJ-OA-08-2026-0108-Supplementary-Table-1.pdf (169.1KB, pdf)
PPJ-OA-08-2026-0108-Supplementary-Table-2,3.pdf (185.5KB, pdf)
PPJ-OA-08-2026-0108-Supplementary-Table-4.pdf (200.5KB, pdf)
PPJ-OA-08-2026-0108-Supplementary-Table-5.pdf (143.6KB, pdf)

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