Verrucarin K

Two new trichothecenes, named 8α-hydroxyroridin H and myrothecin A, along with six known compounds, 8α-acetoxy roridin H, isororidin K, verrucarin A, verrucarin J, verrucarin L and 8α-acetoxy verrucarin L, were isolated from the fermentation broth of a halotolerant fungus Myrothecium sp. GS-17, which was separated from the soil sample of a salina. Structure elucidation and NMR signal assignments were achieved on the basis of spectroscopy. In addition, compounds 1 and 2 were active against plant pathogenic fungi Rhizoctonia solani and Fusarium oxysporum.

There are a large number of valuable substances in diatoms, such as neutral lipid and pigments. However, due to the lack of clear metabolic pathways, their applications are still limited. Recently, chemical modulators are found to be powerful tools to investigate the metabolic pathways of neutral lipids. Thus, in this study, to identify new neutral lipid accumulation effectors, we screened the natural products that we separated before in the model diatom Phaeodactylum tricornutum (P. tricornutum) by using Nile-red staining method. Two compounds, penicillide and verrucarin J which were isolated from two marine fungal strains, were identified to promote neutral lipid accumulation. However, penicillide and verrucarin J were also found to significantly inhibit the growth of P. tricornutum through specifically inhibiting the photosynthesis of P. tricornutum. Quantitative analysis results showed that penicillide and verrucarin J significantly increased total lipid and triacylglycerol (TAG) contents, which are consistent with previous Nile-red staining results. The expression of key genes such as DGAT2D, GPAT2, LPAT2, and PAP involved in TAG synthesis and unsaturated fatty acids also increased after penicillide and verrucarin J treatments. Besides, many TAG-rich plastoglobuli formed in plastids shown by increased lipid droplets in the cytosol. Finally, penicillide and verrucarin J were found to reduce the expression of synthetic genes of fucoxanthin, and consequently reduced the content of fucoxanthin, indicating that there might be crosstalk between lipid metabolism and fucoxanthin metabolism. Thus, our work exhibits two useful compounds that could be used to further study the metabolic pathways of neutral lipid and fucoxanthin, which will fulfill the promise of diatoms as low cost, high value, sustainable feedstock for high-value products such as neutral lipid and pigments.

Microbial flora is investigated to be related with neuropathological conditions in Alzheimer's disease (AD), and is attracting attention as a drug discovery resource. However, the relevance between the soil microbiota and the pathological condition has not been fully clarified due to the difficulty in isolation culture and the component complexity. In this study, we established a library of secondly metabolites produced in microorganism to investigate the potential effect of microorganisms on the production of amyloid β (Aβ), one of the most representative pathogens of AD. We conducted a library screening to quantify Aβ and neuronal toxicity by using cortical neurons from human induced pluripotent stem cells (iPSCs) of AD patients after adding secondary metabolites. Screening results and following assessment of dose-dependency identified Verrucarin A, produced in Myrothecium spp., showed 80% decrease in Aβ production. Furthermore, addition of Mer-A2026A, produced in Streptomyces pactum, showed increase in Aβ42/40 ratio at the low concentration, and decrease in Aβ production at the higher concentration. As a result, established library and iPSC-based phenotyping assay clarified a direct link between Aβ production and soil microorganisms. These results suggest that Aβ-microorganism interaction may provide insight into the AD pathophysiology with potential therapeutics.