RESUMO
Spiroterreusnoids A-F, six undescribed spiro-dioxolane-containing adducts bearing 3,5-dimethylorsellinic acid-based meroterpenoid and 2,3-butanediol moieties were isolated from the endophytic fungus Aspergillus terreus Thom from Tripterygium wilfordii Hook. f. (Celastraceae). The structures of these adducts were established by spectroscopy, single-crystal X-ray diffraction, and experimental electronic circular dichroism (ECD) measurements. Spiroterreusnoids A-F represent the first examples of adducts composed of 3,5-dimethylorsellinic acid-based meroterpenoids. It is noteworthy that spiroterreusnoids A-F possessing a spiro-dioxolane moiety exhibited potential abilities in inhibiting BACE1 (IC50 values ranging from 5.86 to 27.16⯵M) and AchE (IC50 values ranging from 22.18 to 32.51⯵M), while the other analogues without this fragment displayed no such activities. Taken together, spiroterreusnoids A-F represent the first multitargeted natural adducts that could inhibit BACE1 and AchE, and might provide a new template for the development of new anti-Alzheimer's disease drugs.
Assuntos
Acetilcolinesterase/metabolismo , Secretases da Proteína Precursora do Amiloide/antagonistas & inibidores , Ácido Aspártico Endopeptidases/antagonistas & inibidores , Dioxolanos/farmacologia , Inibidores Enzimáticos/farmacologia , Compostos de Espiro/farmacologia , Terpenos/farmacologia , Secretases da Proteína Precursora do Amiloide/metabolismo , Animais , Ácido Aspártico Endopeptidases/metabolismo , Aspergillus/química , Celastraceae/microbiologia , Dioxolanos/química , Dioxolanos/isolamento & purificação , Enguias , Inibidores Enzimáticos/química , Inibidores Enzimáticos/isolamento & purificação , Humanos , Compostos de Espiro/química , Compostos de Espiro/isolamento & purificação , Terpenos/química , Terpenos/isolamento & purificaçãoRESUMO
Several recent studies have lent evidence to the fact that certain so-called plant metabolites are actually biosynthesized by associated microorganisms. In this work, we show that the original source organism(s) responsible for the biosynthesis of the important anticancer and cytotoxic compound maytansine is the endophytic bacterial community harbored specifically within the roots of Putterlickia verrucosa and P. retrospinosa plants. Evaluation of the root endophytic community by chemical characterization of their fermentation products using HPLC-HRMS(n), along with a selective microbiological assay using the maytansine-sensitive type strain Hamigera avellanea revealed the endophytic production of maytansine. This was further confirmed by the presence of AHBA synthase genes in the root endophytic communities. Finally, MALDI-imaging-HRMS was used to demonstrate that maytansine produced by the endophytes is typically accumulated mainly in the root cortex of both plants. Our study, thus, reveals that maytansine is actually a biosynthetic product of root-associated endophytic microorganisms. The knowledge gained from this study provides fundamental insights on the biosynthesis of so-called plant metabolites by endophytes residing in distinct ecological niches.
Assuntos
Endófitos/química , Hidroliases/metabolismo , Maitansina/isolamento & purificação , Aminobenzoatos/metabolismo , Celastraceae/metabolismo , Celastraceae/microbiologia , Cromatografia Líquida de Alta Pressão , Endófitos/metabolismo , Hidroxibenzoatos/metabolismo , Maitansina/química , Maitansina/farmacologia , Estrutura Molecular , Raízes de Plantas/metabolismo , Raízes de Plantas/microbiologia , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por MatrizRESUMO
Maytansinoid compounds are ansa antibiotics occurring in the bacterium Actinosynnema pretiosum, in mosses and in higher plants such as Putterlickia verrucosa (E. Meyer ex Sonder) Szyszyl. The disjunct occurrence of maytansinoids has led to the consideration that plant-associated bacteria may be responsible for the presence of maytansinoids in P. verrucosa plants. Investigation of the bacterial community of this plant by molecular methods led to the observation that A. pretiosum, a maytansine-producing bacterium, is likely to be an inhabitant of the rhizosphere and the endorhiza of P. verrucosa.
Assuntos
Actinomycetales/metabolismo , Celastraceae/química , Maitansina/metabolismo , Raízes de Plantas/metabolismo , Celastraceae/metabolismo , Celastraceae/microbiologia , Maitansina/química , Maitansina/isolamento & purificação , Conformação Molecular , Raízes de Plantas/química , Raízes de Plantas/microbiologiaRESUMO
Three new species of Veronaea, V. ficina on Ficus hispida L. (Moraceae), V. grewiicola on Grewia asiatica L. (Tiliaceae), and V. hippocratiae on Hippocratia arborea Willd. (Celastraceae), collected from forests of Nepal and the Terai belt of North-Eastern Uttar Pradesh, India, are described, illustrated and compared with related taxa.
Assuntos
Celastraceae/microbiologia , Fungos Mitospóricos/isolamento & purificação , Moraceae/microbiologia , Tiliaceae/microbiologia , Fungos Mitospóricos/classificação , Doenças das Plantas/microbiologiaRESUMO
Wood from three different plants of the Celastraceae growing in their natural habitats in Brazil (Maytenus aquifolia Mart.) and South Africa [Putterlickia retrospinosa van Wyk and Mostert, P. verrucosa (E. Meyer ex Sonder) Szyszyl.] was established as a source of endophytic bacteria using a medium selective for actinomycetes. Two isolates were identified as Streptomyces setonii and S. sampsonii whereas two others were not assignable to any of the known Streptomyces species. They were preliminarily named Streptomyces Q21 and Streptomyces MaB-QuH-8. The latter strain produces a new chloropyrrol and chlorinated anthracyclinone. The chloropyrrol showed high activity against a series of multiresistent bacteria and mycobacteria.