Search

Bioherbicides are expected to be a supplement to integrated pest management, assisting in the control of problematic weed species. For instance, bioherbicides (Phoma and BioPhoma) were recently registered in Canada and the USA for the control of some perennial dicotyledonous weeds in lawns. These products are based on strains of the fungus Didymella macrostoma (syn. Phoma macrostoma ) that causes white tip disease (WTD) in Canada thistle ( Cirsium arvense ). In this study, WTD was reported for the first time in the Russian Federation. Analysis of the internal transcribed spacer (ITS) region of nuc rDNA and secondary metabolite profiling confirmed the identity of Russian WTD isolates to Canadian biocontrol strains identified as D. macrostoma . Multilocus phylogenetic analysis based on sequencing of the ITS region, partial large subunit nuc rDNA region (28S), RNA polymerase II second largest subunit gene ( rpb2 ), and partial β-tubulin gene ( tub2 ) has differentiated the WTD isolates from C. arvense and D. macrostoma isolates from other plant hosts. Based on phylogenetic, morphological, and chemotaxonomic features, these WTD isolates were described as a new species named Didymella baileyae , sp. nov. This study also demonstrated the low pathogenicity of the ex-type D. baileyae isolate VIZR 1.53 to C. arvense seedlings and its asymptomatic development in the leaves of aboveground shoots. The organic extracts from mycelium and culture filtrate of D. baileyae , as well as macrocidin A and macrocidin Z, displayed phytotoxicity both to C. arvense leaves and seedlings. Macrocidin A was only detected in the naturally infected leaf tissues of C. arvense showing WTD symptoms. Macrocidins A and Z demonstrated low antimicrobial and cytotoxic activities, exhibiting no entomotoxic properties. The data obtained within this study on the pathogenicity and metabolites of D. baileyae may be important for the rational evaluation of its prospects as a biocontrol agent.

Fungal 10-membered lactones (TMLs), such as stagonolide A, herbarumin I, pinolidoxin, and putaminoxin, are promising candidates for the development of nature-derived herbicides. The aim of this study was to analyze the structure-activity relationships (SAR) of C-9-methyl-substituted TMLs with a multitarget bioassay approach to reveal compounds with useful (phytotoxic, entomotoxic, antimicrobial) or undesirable (cytotoxic) bioactivities. A new TML, stagonolide L ( 1 ), along with five known compounds (stagonolides D ( 2 ) and E ( 3 ), curvulides A ( 4 ) and B 1 /B 2 ( 5a , b ), and pyrenolide C ( 6 )), were purified from cultures of the phytopathogenic fungus Stagonospora cirsii , and five semisynthetic derivatives of 3 and 4 ( 7 - 11 ) were obtained. The absolute configuration of 4 was revised to 2 Z , 4 S , 5 S , 6 R , and 9 R. The identity of 5a , b and stagonolide H is discussed. The phytotoxicity of compound 4 , the entomotoxicity of 5a , b , and nonselective toxicity of compound 6 are demonstrated. The latter confirms the hypothesis that the α,β-unsaturated carbonyl group is associated with the high general toxicity of TML, regardless of its position in the ring and other substituents. The epoxide in compound 4 is important for phytotoxicity. The revealed SAR patterns will be useful for further rational design of TML-based herbicides including curvulide A analogs with a 4,5-epoxy group.

Covering: 2012 to 2022Ten-membered lactones (TMLs) are an interesting and diverse group of natural polyketides that are abundant in fungi and, to a lesser extent, in bacteria, marine organisms, and insects. TMLs are known for their ability to exhibit a wide spectrum of biological activity, including phytotoxic, cytotoxic, antifungal, antibacterial, and others. However, the random discovery of these compounds by scientific groups with various interests worldwide has resulted in patchy information about their distribution among different organisms and their biological activity. Therefore, despite more than 60 years of research history, there is still no common understanding of the natural sources of TMLs, their structural type classification, and most characteristic biological activities. The controversial nomenclature, incorrect or erroneous structure elucidation, poor identification of producing organisms, and scattered information on the biological activity of compounds - all these factors have led to the problems with dereplication and the directed search for TMLs. This review consists of two parts: the first part (Section 2) covers 104 natural TMLs, published between 2012 and 2022 (after the publishing of the previous review), and the second part (Section 3) summarizes information about 214 TMLs described during 1964-2022 and as a result highlights the main problems and trends in the study of these intriguing natural products.

Phytotoxic macrolides attract attention as prototypes of new herbicides. However, their mechanisms of action (MOA) on plants have not yet been elucidated. This study addresses the effects of two ten-membered lactones, stagonolide A (STA) and herbarumin I (HBI) produced by the fungus Stagonospora cirsii , on Cirsium arvense , Arabidopsis thaliana and Allium cepa . Bioassay of STA and HBI on punctured leaf discs of C. arvense and A. thaliana was conducted at a concentration of 2 mg/mL to evaluate phenotypic responses, the content of pigments, electrolyte leakage from leaf discs, the level of reactive oxygen species, Hill reaction rate, and the relative rise in chlorophyll a fluorescence. The toxin treatments resulted in necrotic and bleached leaf lesions in the dark and in the light, respectively. In the light, HBI treatment caused the drop of carotenoids content in leaves on both plants. The electrolyte leakage caused by HBI was light-dependent, in contrast with that caused by STA. Both compounds induced light-independent peroxide generation in leaf cells but did not affect photosynthesis 6 h after treatment. STA (10 µg/mL) caused strong disorders in root cells of A. thaliana leading to the complete dissipation of the mitochondrial membrane potential one hour post treatment, as well as DNA fragmentation and disappearance of acidic vesicles in the division zone after 8 h; the effects of HBI (50 µg/mL) were much milder. Furthermore, STA was found to inhibit mitosis but did not affect the cytoskeleton in cells of root tips of A. cepa and C. arvense , respectively. Finally, STA was supposed to inhibit the intracellular vesicular traffic from the endoplasmic reticulum to the Golgi apparatus, thus interfering with mitosis. HBI is likely to have another main MOA, probably inhibiting the biosynthesis of carotenoids.

Ten-membered lactones (nonenolides) demonstrate phytotoxic, antimicrobial, and fungicidal activity promising for the development of natural product-derived pesticides. The fungus Stagonospora cirsii is able to produce phytotoxic stagonolides A ( 1 ), J ( 2 ), K ( 3 ) and herbarumin I ( 4 ) with high yield. The aim of this study was to create a set of structurally related nonenolides and to reveal the structural features that affect their biological activity. Stagonolide A ( 1 ) and C-7 oxidized stagonolide K ( 11 ) showed the highest phytotoxicity in leaf puncture assay and agar seedlings assay. The oxidation of C-7 hydroxyl group (as in 1 , acetylstagonolide A ( 10 ) and ( 11 ) led to the manifestation of toxicity to microalgae, Bacillus subtilis and Sf9 cells regardless of the configuration of C-9 propyl chains ( R in 1 and 10 , S in 11 ). C-7 non-oxidized nonenolides displayed none or little non-target activity. Notably, 7 S compounds were more phytotoxic than their 7 R analogues. Due to the high inhibitory activity against seedling growth and the lack of side toxicity, mono- and bis(acetyl)- derivatives of herbarumin I were shown to be potent for the development of pre-emergent herbicides. The identified structural features can be used for the rational design of new herbicides.

The study of fungal antibiotics in their competitive interactions with arthropods may lead to the development of novel biorational insecticides. Extracts of Alternaria tenuissima MFP253011 obtained using various methods showed a wide range of biological activities, including entomotoxic properties. Analysis of their composition and bioactivity allowed us to reveal several known mycotoxins and unidentified compounds that may be involved in the entomotoxic activity of the extracts. Among them, tenuazonic acid (TeA), which was the major component of the A. tenuissima extracts, was found the most likely to have larvicidal activity against Galleria mellonella . In the intrahaemocoel injection bioassay, TeA was toxic to G. mellonella and of Zophobas morio with an LT 50 of 6 and 2 days, respectively, at the level of 50 µg/larva. Administered orally, TeA inhibited the growth of G. mellonella larvae and caused mortality of Acheta domesticus adults (LT 50 7 days) at a concentration of 250 µg/g of feed. TeA showed weak contact intestinal activity against the two phytophages, Tetranychus urticae and Schizaphis graminum , causing 15% and 27% mortality at a concentration of 1 mg/mL, respectively. TeA was cytotoxic to the Sf9 cell line (IC 50 25 µg/mL). Thus, model insects such as G. mellonella could be used for further toxicological characterization of TeA.

The use of many fungal phytotoxins as natural herbicides is still limited because they cannot penetrate leaf cuticle without injury and a little is known on their selectivity. In order to assess the herbicidal potential of phytotoxic 10-membered lactones (stagonolide A, stagonolide K, and herbarumin I), the selection of adjuvants, the evaluation of selectivity of the toxins and the efficacy of their formulations were performed. Among four adjuvants tested, Hasten™ (0.1%, v / v ) increased phytotoxic activity of all the toxins assayed on non-punctured leaf discs of Sonchus arvensis . When assayed on intact leaf fragments of 18 plants species, 10 species were low to moderately sensitive to stagonolide A, while just five and three species were sensitive to stagonolide K and herbarumin I, respectively. Both leaf damage or addition of Hasten™ (0.1%) to the formulations of the compounds considerably increased or altered the sensitivity of plants to the toxins. Stagonolide A was shown to be non-selective phytotoxin. The selectivity profile of stagonolide K and herbarumin I depended on the leaf wounding or the adjuvant addition. Stagonolide A and herbarumin I formulated in 0.5% Hasten™ showed considerable herbicidal effect on S. arvensis aerial shoots. This study supported the potential of the oil-based adjuvant Hasten™ to increase the herbicidal efficacy of natural phytotoxins.

The fungus, Alternaria sonchi is considered to be a potential agent for the biocontrol of perennial sowthistle ( Sonchus arvensis ). A new chlorinated xanthone, methyl 8-hydroxy-3-methyl-4-chloro-9-oxo-9 H -xanthene-1-carboxylate ( 1 ) and a new benzophenone derivative, 5-chloromoniliphenone ( 2 ), were isolated together with eleven structurally related compounds ( 3 - 13 ) from the solid culture of the fungus, which is used for the production of bioherbicidal inoculum of A. sonchi . Their structures were determined by spectroscopic (mostly by NMR and MS) methods. Alternethanoxins A and B, which were reported in A. sonchi earlier, were re-identified as moniliphenone and pinselin, respectively. The isolated compounds were tested for phytotoxic, antimicrobial, insecticidal, cytotoxic and esterase-inhibition activities. They did not demonstrate high phytotoxicity (lesions up to 2.5 mm in diameter/length at a concentration of 2 mg/mL) when tested on leaf disks/segments of perennial sowthistle ( Sonchus arvensis ) and couch grass ( Elytrigia repens ). They did not possess acute toxicity to Paramecium caudatum , and showed moderate to low cytotoxicity (IC 50 > 25 µg/mL) for U937 and K562 tumor cell lines. However, chloromonilicin and methyl 3,8-dihydroxy-6-methyl-4-chloro-9-oxo-9 H -xanthene-1-carboxylate ( 4 ) were shown to have antimicrobial properties with MIC 0.5-5 µg/disc. Compound 4 and chloromonilinic acid B were found to have contact insecticidal activity to wheat aphid ( Schizaphis graminum ) at 1 mg/mL. Compounds 2 and methyl 3,8-dihydroxy-6-methyl-9-oxo-9 H -xanthene-1-carboxylate displayed selective carboxylesterase inhibition activity at concentration of 100 µg/mL. Therefore, the waste solid substrate for production of A. sonchi spores can be re-utilized for the isolation of a number of valuable natural products.

Two new natural 10-membered macrolides ( 1 , 2 ) and one chromene-4,5-dione derivative ( 3 ), named stagonolides J and K and stagochromene A, respectively, were isolated from the phytopathogenic fungus Stagonospora cirsii S-47, together with two known compounds, stagonolide A ( 4 ) and herbarumin I ( 5 ). Stagonolides J and K and stagochromene A were characterized as (5 E ,7 R *,8 S *,9 R *)-7,8-dihydroxy-9-propyl-5-nonen-9-olide, (5 E ,7 R ,9 S )-7-hydroxy-9-propyl-5-nonen-9-olide, and (2 R *,3 R *)-3-hydroxy-2-propyltetrahydro-2 H -chromene-4,5(3 H ,4a H )-dione, respectively, by spectroscopic (mostly by NMR and ESIMS) data. Compounds 1 - 5 showed different rates of phytotoxic activity on punctured leaf discs of Sonchus arvensis . The antimicrobial, cytotoxic, and antiprotozoal activity of isolated compounds was also evaluated. Based on our data, stagonolide K and herbarumin I can be proposed as a potential scaffold for the development of a new natural herbicide and estimated as possible selection/quality markers of a bioherbicide based on S. cirsii , while stagonolide A can be considered as a mycotoxin.