Butyrolactones,inhibitors of 5-lipoxygenase from fungal metabolites

In our ongoing search for new inhibitors of 5-lipoxygenase（5-LOX） from microbial resources,Aspergillus F06Z-509 was found to produce active components.Three active compounds named F06Z-509-A,B and C were obtained and identified as butyrolactoneⅡ,ⅠandⅢby NMR and MS data analyses.They showed inhibitory activity against 5-LOX with IC50 of 21.43, 22.51 and 11.83μg/mL,respectively.Butyrolactones are shown to be inhibitors of 5-LOX for the first time.

Fungal pyrrolidine-containing metabolites inhibit alkaline phosphatase activity in bone morphogenetic protein-stimulated myoblastoma cells

Fibrodysplasia ossificans progressiva(FOP)is a rare autosomal dominant congenital disorder characterized by progressive heterotopic ossification in muscle tissues.A constitutively activated mutation of a bone morphogenetic protein(BMP)receptor,ALK2,has been identified in patients with FOP.We report here that four structurally related compounds,lucilactaene,hydroxylucilactaene,NG-391 and NG-393,produced by fungal strain Fusarium sp.B88,inhibit BMP signaling in vitro.Alkaline phosphatase activity,a marker enzyme of osteoblastic differentiation,was decreased in C2C12 myoblasts stably expressing mutant ALK2 by treatment with those compounds with IC_(50) values of 5.7,6.8,6.9 and 6.1 mM,respectively.Furthermore,NG-391 and NG-393 inhibited BMP-specific luciferase reporter activity,which is directly regulated by transcription factor Smads,with IC50 values of 1.4 and 2.1 mM,respectively.These findings suggest that these fungal metabolites may provide a new direction in the development of FOP therapeutics.

Effect of Crude Drug Extracts on Trypacidin Production in Aspergillus fumigatus

We examined the production of fungal metabolites as biological responses to 120 crude drugs by culturing the filamentous fungus Aspergillus fumigatus CBS101355 with crude drugs and analyzing the culture extracts by HPLC. Nine crude drug extracts [Kyokatsu (Notopterygium), Kyonin (apricot kernel), Kujin (Sophora root), Goboshi (Burdock fruit), Goma (sesame), Shokyo (ginger), Shin’i (magnolia flower), Togashi (Benincasa seed), and Bukuryo (Poria sclerotium)] induced the production of trypacidin, which was not produced by culturing in potato dextrose broth without crude drugs.

Fusarium-produced vitamin B6 promotes the evasion of soybean resistance by Phytophthora sojae

Plants can be infected by multiple pathogens concurrently in natural systems. However,pathogen–pathogen interactions have rarely been studied. In addition to the oomycete Phytophthora sojae, fungi such as Fusarium spp. also cause soybean root rot. In a 3-year field investigation, we discovered that P. sojae and Fusarium spp. frequently coexisted in diseased soybean roots. Out of 336 P. sojae–soybean–Fusarium combinations,more than 80% aggravated disease. Different Fusarium species all enhanced P. sojae infection when co-inoculated on soybean. Treatment with Fusarium secreted non-proteinaceous metabolites had an effect equal to the direct pathogen coinoculation. By screening a Fusarium graminearum mutant library, we identified Fusarium promoting factor of Phytophthora sojae infection 1(Fpp1),encoding a zinc alcohol dehydrogenase. Fpp1 is functionally conserved in Fusarium and contributes to metabolite-mediated infection promotion, in which vitamin B6(VB6) produced by Fusarium is key. Transcriptional and functional analyses revealed that Fpp1 regulates two VB6 metabolism genes, and VB6 suppresses expression of soybean disease resistance-related genes. These results reveal that co-infection with Fusarium promotes loss of P. sojae resistance in soybean, information that will inform the sustainable use of diseaseresistant crop varieties and provide new strategies to control soybean root rot.