Yan-Li Wang

Nematodetoxic aurovertin-type metabolites from a root-knot nematode parasitic fungus Pochonia chlamydosporia.

Chemical investigation of one fungal strain P. chlamydosporia YMF 1.00613 isolated from root knots of tobacco infected by Meloidogyne incognita led to the isolation and identification of four aurovertin-type metabolites, which include a new compound, aurovertin I (A1), and three known metabolites, aurovertins E, F and D (A2-A4). Their structures were established by spectroscopic studies such as 1D- and 2D-NMR and MS analysis. Aurovertin I (A1) is the first natural product with an aurovertin skeleton with one less carbon. Compounds A3 and A4 showed the toxicity to the worms of the free-living nematode Panagrellus redivevus with the LC(50) values 88.6 and 41.7 microg/mL at 48 h, respectively. All four aurovertins did not show obvious inhibitory effects on egg hatch of root knot nematode Meloidogyne incognita. The results suggested that the aurovertin-type metabolites produced by P. chlamydosporia might be one of the pathogenic factors involved in the suppression of nematodes.

Isolation of putative biosynthetic intermediates of prenylated indole alkaloids from a thermophilic fungus Talaromyces thermophilus.

The putative key biosynthetic intermediates of prenylated indole alkaloids have long been proposed but never isolated. Two such alkaloids, named talathermophilins A and B (1 and 2), were isolated from a thermophilic fungus Talaromyces thermophilus strain YM1-3 and were identified by NMR and MS spectroscopic analyses. The ratio of 1 and 2 in the culture broths was unexpectedly rather constant (about 2:3), which even remained unchanged despite the addition of exogenous 1 or 2, suggesting that talathermophilins might be of special function for the extremophilic fungus.

Thermolides, potent nematocidal PKS-NRPS hybrid metabolites from thermophilic fungus Talaromyces thermophilus.

Macrocyclic PKS-NRPS hybrid metabolites represent a unique family of natural products mainly from bacteria with broad and outstanding biological activities. However, their distribution in fungi has rarely been reported, and little has been reported regarding their nematocidal activity. Here we describe an unprecedented class of PKS-NRPS hybrid metabolites possessing a 13-membered lactam-bearing macrolactone, thermolides A-F (1-6) from a thermophilic fungus Talaromyces thermophilus. We showed that 1 and 2 displayed potent inhibitory activity against three notorious nematodes with LC(50) values of 0.5-1 μg/mL, as active as commercial avermectins. This work provided a new class of promising lead compounds for nematocide discovery.

Arthrobotrisins A–C, Oligosporons from the Nematode-Trapping Fungus Arthrobotrys oligospora

Arthrobotrys oligospora is a carnivorous fungus that can use mycelia trapping devices to capture their prey. Three novel oligosporons, named arthrobotrisins A-C (1-3), were isolated from A. oligospora and identified by spectroscopic analysis in combination with X-ray diffraction. This is the first time that the relative configuration of naturally occurring oligosporon metabolites has been fully determined. Compound 3 exhibited specific antibacterial activities.

Isolation of talathermophilins from the thermophilic fungus Talaromyces thermophilus YM3-4.

Six indole alkaloids with various levels of prenylation were isolated from the thermophilic fungus Talaromyces thermophilus strain YM3-4. Their structures were identified by NMR and MS spectroscopic analyses. Compounds 1 and 2 are new analogues of the key versatile precursor notoamide E. Compound 3 is a novel analogue of preechinulin, and compound 4 was reported as a natural occurring cyclo(glycyltryptophyl) for the first time. The metabolite profile of this thermophilic organism displayed a biosynthetic pathway for talathermophilins.

Yellow Pigment Aurovertins Mediate Interactions between the Pathogenic Fungus Pochonia chlamydosporia and Its Nematode Host.

Nematophagous fungi are globally distributed soil fungi and well-known natural predators of soil-dwelling nematodes. Pochonia chlamydosporia can be found in diverse nematode-suppressive soils as a parasite of nematode eggs and is one of the most studied potential biological control agents of nematodes. However, little is known about the functions of small molecules in the process of infection of nematodes by this parasitic fungus or about small-molecule-mediated interactions between the pathogenic fungus and its host. Our recent study demonstrated that a P. chlamydosporia strain isolated from root knots of tobacco infected by the root-knot nematode Meloidogyne incognita produced a class of yellow pigment metabolite aurovertins, which induced the death of the free-living nematode Panagrellus redivevus. Here we report that nematicidal P. chlamydosporia strains obtained from the nematode worms tended to yield a total yellow pigment aurovertin production exceeding the inhibitory concentration shown in nematicidal bioassays. Aurovertin D was abundant in the pigment metabolites of P. chlamydosporia strains. Aurovertin D showed strong toxicity toward the root-knot nematode M. incognita and exerted profound and detrimental effects on the viability of Caenorhabditis elegans even at a subinhibitory concentration. Evaluation of the nematode mutation in the β subunit of F1-ATPase, together with the application of RNA interference in screening each subunit of F1FO-ATPase in the nematode worms, demonstrated that the β subunit of F1-ATPase might not be the specific target for aurovertins in nematodes. The resistance of C. elegans daf-2(e1370) and the hypersensitivity of C. elegans daf-16(mu86) to aurovertin D indicated that DAF-16/FOXO transcription factor in nematodes was triggered in response to the aurovertin attack. These findings advance our understanding of the roles of aurovertin production in the interactions between nematodes and the pathogen fungus P. chlamydosporia.

Metabolites from carnivorous fungus Arthrobotrys entomopaga and their functional roles in fungal predatory ability.

The carnivorous fungus Arthrobotrys entomopaga (Drechsler) can develop adhesive knobs to capture nematodes. Chemical study on the culture medium of A. entomopaga producing adhesive knobs led to isolation of six trace amounts of metabolites, including two new metabolites, paganins A and B (1 and 2), blumenol A (3), talathermophilins A and B (4 and 5), and cyclo(glycyltryptophyl) (6). Compounds 3-6 were reported for the first time from carnivorous fungi. Compounds 1 and 2 promoted the formation of the predatory adhesive knobs with an increasing rate up to 118% at a concentration of 50 μM but showed moderate inhibitory activity at a concentration of 5 μM. Moreover, compounds 1 and 2 displayed strong inhibitory activities toward the formation of A. entomopaga conidiophores with inhibitory rates of 40-75%. Growth experiments suggested that compounds 1 and 2 could be involved in the regulation of the fungal predatory and reproductive abilities. Nematode chemotaxis bioassay indicated that compounds 1 and 3 displayed strong nematode-attracting abilities. These findings provided a new type of regulatory metabolite and support for the hypothesis that predators often evolve to respond to their metazoan prey.

Morphology Regulatory Metabolites from Arthrobotrys oligospora

Novel autoregulatory metabolites, arthrosporols A-C (1-3), involved in regulating the morphological switch in fungi, were purified and characterized from the carnivorous fungus Arthrobotrys oligospora. These compounds possess a novel hybrid carbon skeleton consisting of an epoxy-cyclohexenol combined with a rare monocyclic sesquiterpenol substructure. This is the first report of a monocyclic sesquiterpenol of this type of fungal origin. Compounds 1-3 displayed significant inhibitory activities toward the formation of conidiophores, while compounds 1 and 3 showed the opposite effects on the formation of a two-dimensional network with increasing rates of 40-90% and inhibiting rates of 30-90%, respectively.

Regulation of the Growth of Cotton Bollworms by Metabolites from an Entomopathogenic Fungus Paecilomyces cateniobliquus

Chemical investigation of one entomopathogenic fungus Paecilomyces cateniobliquus YMF1.01799 led to the isolation and identification of six metabolites, which include three new compounds (2-3, and 5) and three known metabolites. Their structures were established by spectroscopic studies such as 1D and 2D NMR and MS analysis. Insect growth experiments suggested that polyketide-derived compound 1 showed significant inhibitory effect on the growth of cotton bollworm Helicoverpa armigera, while terpenoid-derived metabolite 5 promoted the growth of the larvae. The findings revealed that the entomopathogenic fungus P. cateniobliquus could produce different types of metabolites to regulate growth of the insect.