validamycin-a and validamycins

The general cutworm, Spodoptera litura (Lepidoptera: Noctuidae) is a worldwide destructive omnivorous pest and the endoparasitoid wasp Meteorus pulchricornis (Hymenoptera: Braconidae) is the dominant endoparasitoid of S. litura larvae. Trehalase is a key enzyme in insect trehalose metabolism and plays an important role in the growth and development of insects. However, the specific function of trehalase in parasitoid and host associations has been less reported. In this study, we obtained two trehalase genes (SlTre1 and SlTre2) from our previously constructed S. litura transcriptome database; they were highly expressed in 3rd instar larvae. SlTre1 was mainly expressed in the midgut, and SlTre2 was expressed highest in the head. SlTre1 and SlTre2 were highly expressed 5 days after parasitization by M. pulchricornis. Treatment with the trehalase inhibitor validamycin A significantly inhibited the expression levels of SlTre1 and SlTre2, and the trehalase activity. Besides, the content of trehalose was increased but the content of glucose was decreased 24 h after validamycin A treatment in parasitized S. litura larvae. In addition, the immune-related genes in phenoloxidase (PO) pathway and fatty acid synthesis-related genes in lipid metabolism were upregulated in parasitized host larvae after validamycin A treatment. Importantly, the emergence rate, proportion of normal adults, and body size of parasitoid offspring was decreased in parasitized S. litura larvae after validamycin A treatment, indicating that validamycin A disrupts the trehalose metabolism of parasitized host and thus reduces the fitness of parasitoid offspring. The present study provides a novel perspective for coordinating the application of biocontrol and antibiotics in agroecosystem.

Topics: Animals; Carbohydrate Metabolism; Larva; Trehalase; Trehalose

Validamycin A (VAL-A) is a widely used antifungal antibiotic for the treatment of sheath blight disease of rice and other plants. It can be produced from agro-industrial by-products by Streptomyces hygroscopicus 5008. To enhance its production titer, in this work, the entire val gene cluster was amplified in tandem in S. hygroscopicus 5008 by integrating the zouA-mediated DNA amplification system into between the two boundaries of val gene cluster, resulting in multiple copies (mainly three to five) of the val gene cluster. The genetic stability of the amplified copies was confirmed by Southern blot and fermentation experiments. In shake flask fermentation, the recombinant strain (TC03) led to a 34% enhancement of VAL-A production titer compared to that of the wild-type strain, while the accumulation of intermediate validoxylamine A was decreased in TC03. Additionally, both the structural gene transcription levels and the ValG enzyme activity were significantly increased in TC03. This work demonstrated that the amplification of the val gene cluster was an efficient strategy to enhance VAL-A production by S. hygroscopicus 5008, and the information obtained would be helpful for engineering other interesting antibiotic biosynthesis by gene cluster amplification.

Topics: Inositol; Multigene Family; Streptomyces

All Basidiomycotina screened were sensitive to validamycin A, whereas most Ascomycotina and all Mucorales and Oomycetes were insensitive. Studies with Rhizoctonia cerealis and Fusarium culmorum showed that, in semi-solid culture, the antibiotic caused a decrease in colony radial growth rate and that this was associated with a decrease in mean hyphal extension rate and an increase in hyphal branching. However, the antibiotic did not alter the morphology of R. cerealis grown in liquid culture (shaken or stationary). Validamycin A caused a reduction in the number and viability of conidia produced by F. culmorum.

Topics: Antifungal Agents; Drug Resistance, Microbial; Fungi; Fusarium; Inositol; Mitosporic Fungi; Rhizoctonia; Spores, Fungal