Defensive Specialized Metabolites from the Latex of Euphorbia jolkinii.

Plant latex is sequestered in laticiferous structures and exuded immediately from damaged plant tissues. The primary function of plant latex is related to defense responses to their natural enemies. Euphorbia jolkinii Boiss. is a perennial herbaceous plant that greatly threaten the biodiversity and ecological integrity of northwest Yunnan, China. Nine triterpenes (1-9), four non-protein amino acids (10-13) and three glycosides (14-16) including a new isopentenyl disaccharide (14), were isolated and identified from the latex of E. jolkinii. Their structures were established on the basis of comprehensive spectroscopic data analyses. Bioassay revealed that meta-tyrosine (10) showed significant phytotoxic activity, inhibiting root and shoot growth of Zea mays, Medicago sativa, Brassica campestris, and Arabidopsis thaliana, with EC50 values ranging from 4.41 ± 1.08 to 37.60 ± 3.59 µg/mL. Interestingly, meta-tyrosine inhibited the root growth of Oryza sativa, but promoted their shoot growth at the concentrations below 20 µg/mL. meta-Tyrosine was found to be the predominant constituent in polar part of the latex extract from both stems and roots of E. jolkinii, but undetectable in the rhizosphere soil. In addition, some triterpenes showed antibacterial and nematicidal effects. The results suggested that meta-tyrosine and triterpenes in the latex might function as defensive substances for E. jolkinii against other organisms.

Immunosuppressive and Adipogenesis Inhibitory Sesterterpenoids with a Macrocyclic Ether System from Eurysolen gracilis.

Eurysoloids A (1) and B (2), two novel diastereomeric sesterterpenoids possessing a pentacyclic 5/6/5/10/5 framework with an unusual macrocyclic ether system, were isolated from Eurysolen gracilis Prain. Their structures were unambiguously determined by spectroscopic, single-crystal X-ray diffraction and DP4+ analyses. A plausible biosynthetic pathway for compounds 1 and 2 was proposed. Both compounds exhibited immunosuppressive activity via inhibiting the production of cytokine IFN-γ of T cells, and compound 2 inhibited adipogenesis in 3T3-L1 adipocytes.

Novel Polyketide-Terpenoid Hybrid Metabolites from a Potent Nematicidal Arthrobotrys oligospora Mutant ΔAOL_s00215g278.

Here, we reported that detailed investigation on trace targeted metabolites from nematode-trapping fungus Arthrobotrys oligospora mutant with deletion of P450 gene AOL_s00215g278 led to isolation of 9 new polyketide-terpenoid hybrid derivatives, including four new glycosides of the key precursor farnesyl hydrotoluquinol (1) and, surprisingly, four new sesquiterpenyl epoxy-cyclohexenoids (SECs) analogues. Among them, two major target metabolites 1 and 14 displayed moderate nematode inhibitory ability. Moreover, the mutant lacking AOL_s00215g278 could form far more nematode-capturing traps within 6 h in contact with nematodes and show rapid potent nematicidal activity with killing 93.7% preys, though deletion of the P450 gene resulted in dramatic decrease in fungal colony growth and failure to produce fungal conidia. The results unequivocally revealed that gene AOL_s00215g278 should be involved in not only the SEC biosynthetic pathway in the nematode-trapping fungus A. oligospora but also fungal conidiation and nematicidal activity.

Leucosceptroid B from glandular trichomes of Leucosceptrum canum reduces fat accumulation in Caenorhabditis elegans through suppressing unsaturated fatty acid biosynthesis.

Obesity that is highly associated with numerous metabolic diseases has become a global health issue nowdays. Plant sesterterpenoids are an important group of natural products with great potential; thus, their bioactivities deserve extensive exploration. RNA-seq analysis indicated that leucosceptroid B, a sesterterpenoid previously discovered from the glandular trichomes of Leucosceptrum canum, significantly regulated the expression of 10 genes involved in lipid metabolism in Caenorhabditis elegans. Furthermore, leucosceptroid B was found to reduce fat storage, and downregulate the expression of two stearoyl-CoA desaturase (SCD) genes fat-6 and fat-7, and a fatty acid elongase gene elo-2 in wild-type C. elegans. In addition, leucosceptroid B significantly decreased fat accumulation in both fat-6 and fat-7 mutant worms but did not affect the fat storage of fat-6; fat-7 double mutant. These findings indicated that leucosceptroid B reduced fat storage depending on the downregulated expression of fat-6, fat-7 and elo-2 and thereby inhibiting the biosynthesis of the corresponding unsaturated fatty acid. These findings provide new insights into the development and utilization of plant sesterterpenoids as potential antilipemic agents.

Selected Mutations Revealed Intermediates and Key Precursors in the Biosynthesis of Polyketide-Terpenoid Hybrid Sesquiterpenyl Epoxy-cyclohexenoids.

Sesquiterpenyl epoxy-cyclohexenoids (SECs) show impressive biological activities. However, the key pathways for SECs still remain unambiguous. Unexpectedly, 11 new SECs and derivatives with diverse oxidation patterns were isolated after the deletion of gene 274. A high accumulation of toluquinol and its new glycosides in mutant Δ276 and further isolation of the most crucial precursors farnesyl hydroquinone, farnesyl quinone, and three new derivatives from mutant Δ278 confirm that farnesylation at toluquinol is the key step for SECs.