Dataset Information

Characterization of the biosynthetic genes for 10,11-dehydrocurvularin, a heat shock response-modulating anticancer fungal polyketide from Aspergillus terreus.

ABSTRACT: 10,11-Dehydrocurvularin is a prevalent fungal phytotoxin with heat shock response and immune-modulatory activities. It features a dihydroxyphenylacetic acid lactone polyketide framework with structural similarities to resorcylic acid lactones like radicicol or zearalenone. A genomic locus was identified from the dehydrocurvularin producer strain Aspergillus terreus AH-02-30-F7 to reveal genes encoding a pair of iterative polyketide synthases (A. terreus CURS1 [AtCURS1] and AtCURS2) that are predicted to collaborate in the biosynthesis of 10,11-dehydrocurvularin. Additional genes in this locus encode putative proteins that may be involved in the export of the compound from the cell and in the transcriptional regulation of the cluster. 10,11-Dehydrocurvularin biosynthesis was reconstituted in Saccharomyces cerevisiae by heterologous expression of the polyketide synthases. Bioinformatic analysis of the highly reducing polyketide synthase AtCURS1 and the nonreducing polyketide synthase AtCURS2 highlights crucial biosynthetic programming differences compared to similar synthases involved in resorcylic acid lactone biosynthesis. These differences lead to the synthesis of a predicted tetraketide starter unit that forms part of the 12-membered lactone ring of dehydrocurvularin, as opposed to the penta- or hexaketide starters in the 14-membered rings of resorcylic acid lactones. Tetraketide N-acetylcysteamine thioester analogues of the starter unit were shown to support the biosynthesis of dehydrocurvularin and its analogues, with yeast expressing AtCURS2 alone. Differential programming of the product template domain of the nonreducing polyketide synthase AtCURS2 results in an aldol condensation with a different regiospecificity than that of resorcylic acid lactones, yielding the dihydroxyphenylacetic acid scaffold characterized by an S-type cyclization pattern atypical for fungal polyketides.

SUBMITTER: Xu Y

PROVIDER: S-EPMC3592213 | biostudies-literature | 2013 Mar

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Characterization of the biosynthetic genes for 10,11-dehydrocurvularin, a heat shock response-modulating anticancer fungal polyketide from Aspergillus terreus.

Xu Yuquan Y Espinosa-Artiles Patricia P Schubert Vivien V Xu Ya-ming YM Zhang Wei W Lin Min M Gunatilaka A A Leslie AA Süssmuth Roderich R Molnár István I

Applied and environmental microbiology 20130118 6

10,11-Dehydrocurvularin is a prevalent fungal phytotoxin with heat shock response and immune-modulatory activities. It features a dihydroxyphenylacetic acid lactone polyketide framework with structural similarities to resorcylic acid lactones like radicicol or zearalenone. A genomic locus was identified from the dehydrocurvularin producer strain Aspergillus terreus AH-02-30-F7 to reveal genes encoding a pair of iterative polyketide synthases (A. terreus CURS1 [AtCURS1] and AtCURS2) that are pred ...[more]

PMID: 23335766

Similar Datasets

Project description:BackgroundThe overuse of antibiotics leads to the emergence of antibiotic-resistant microbes which causes high mortality worldwide. Therefore, the synthesis of new active compounds has multifunctional activities are the main challenge. Nanotechnology provides a solution for this issue.MethodThe endophytic fungal strain Aspergillus terreus BR.1 was isolated from the healthy root of Allium sativum and identified using internal transcribed spacer (ITS) sequence analysis. The copper oxide nanoparticles (CuO-NPs) were synthesized by harnessing the metabolites of the endophytic fungal strain. The UV-Visble spectroscopy, Fourier-transform infrared spectroscopy (FT-IR), Transmission electron micrscopy (TEM), Energy dispersive X-ray (EDX), X-ray diffraction (XRD), Dynamic light scattering (DLS), and zeta potential (ζ) were used for the characterization of synthesized CuO-NPs. The activity against different pathogenic bacteria and Candida species were investigated by agar well-diffusion method. The biocombatibility and anticancer activity were assessed by MTT assay method. The scavenging of DPPH was used to investigate the antioxidant activity of synthesized CuO-NPs.ResultsData showed the successful formation of crystalline nature and spherical shape CuO-NPs with sizes in the ranges of 15-55 nm. The EDX reveals that the as-formed sample contains ions of C, O, Cl, and Cu with weight percentages of 18.7, 23.82, 11.31, and 46.17%, respectively. The DLS and ζ-potential showed high homogeneity and high stability of synthesized CuO-NPs with a polydispersity index (PDI) of 0.362 and ζ-value of - 26.6 mV. The synthesized CuO-NPs exhibited promising antibacterial and anti-Candida activity (concentration-dependent) with minimum inhibitory concentration (MIC) values in the ranges of 25-50 µg mL-1. Moreover, the fungal mediated-CuO-NPs targeted cancer cells of MCF7 and PC3 at low IC50 concentrations of 159.2 ± 4.5 and 116.2 ± 3.6 µg mL-1, respectively as compared to normal cells (Vero and Wi38 with IC50 value of 220.6 ± 3.7 and 229.5 ± 2.1 µg mL-1, respectively). The biosynthesized CuO-NPs showed antioxidant activity as detected by the DPPH method with scavenging percentages of 80.5 ± 1.2% at a concentration of 1000 µg mL-1 and decreased to 20.4 ± 4.2% at 1.9 µg mL-1 as compared to ascorbic acid (control) with scavenging activity of 97.3 ± 0.2 and 37.5 ± 1.3% at the same concentrations, respectively.ConclusionThe fungal mediated-CuO-NPs exhibited promising activity and can be integrated into various biomedical and theraputic applications.

Dataset Information

Characterization of the biosynthetic genes for 10,11-dehydrocurvularin, a heat shock response-modulating anticancer fungal polyketide from Aspergillus terreus.

Publications

Characterization of the biosynthetic genes for 10,11-dehydrocurvularin, a heat shock response-modulating anticancer fungal polyketide from Aspergillus terreus.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets