Uncovering production of specialized metabolites by Streptomyces argillaceus by activating cryptic biosynthesis gene clusters
Ontology highlight
ABSTRACT:
PROVIDER: PRJEB25498 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Sequencing of Streptomyces genomes has revealed they harbor a high number of biosynthesis gene cluster (BGC), which uncovered their enormous potentiality to encode specialized metabolites. However, these metabolites are not usually produced under standard laboratory conditions. In this manuscript we report the activation of BGCs for antimycins, carotenoids, germicidins and desferrioxamine compounds in Streptomyces argillaceus, and the identification of the encoded compounds. This was achieved by following different strategies, including changing the growth conditions, heterologous expression of the cluster and inactivating the adpAa or overexpressing the abrC3 global regulatory genes. In addition, three new carotenoid compounds have been identified.
| S-EPMC5993118 | biostudies-literature
Project description:ArcZ regulation of specialized metabolites
| PRJEB33827 | ENA
Project description:Filamentous fungi produce a vast array of secondary metabolites (SMs) and some of them are applied in agriculture or pharmacology. Recent sequencing of the rice pathogen Fusarium fujikuroi revealed the presence of far more SM-encoding genes than known products. SM production is energy-consuming and thus tightly regulated, leaving the majority of SM gene clusters silent under laboratory conditions. It is now well established that one important regulatory layer in SM biosynthesis involves histone modifications that render the genes either silent or poised for transcription. In this study, we show that the majority of the putative SM gene clusters in F. fujikuroi are located within facultative heterochromatin marked by H3K27me3. In this study, we performed comparative transcriptomics of a knock-down mutant of the responsible methyltransferase Kmt6 involved in H3K27 methylation grown on either solid complete medium or solid synthetic ICI medium. Overall four so far cryptic and otherwise silent putative SM gene clusters were significantly induced in the KMT6kd strain accompanied by reduced H3K27me3 levels at the respective gene loci and accumulation of novel metabolites. One of the four putative SM gene clusters, the STC5 gene cluster, was analysed in detail and heterologous expression of the key enzyme allowed for the identification of the first pathway-specific intermediate (1R,4R,5S)-guaia-6,10(14)-diene. 2 strains were analysed in overall two conditions, and each with 3 biological replicates
2016-07-04 | E-GEOD-80477 | biostudies-arrayexpress
Project description:While specialized metabolites are thought to mediate ecological interactions, the evolutionary processes driving chemical diversification, particularly among closely related lineages, remain poorly understood. Here, we examine the evolutionary dynamics governing the distribution of natural product biosynthetic gene clusters (BGCs) among 118 strains representing all nine currently named species of the marine actinobacterial genus Salinispora. While much attention has been given to the role of horizontal gene transfer (HGT) in structuring BGC distributions, we find that vertical descent facilitates interspecies BGC diversification over evolutionary timescales. Moreover, we identified a distinct phylogenetic signal among Salinispora species at both the BGC and metabolite level, indicating that specialized metabolism represents a conserved phylogenetic trait. Using a combination of genomic analyses and liquid chromatography-high-resolution tandem mass spectrometry (LC-MS/MS) targeting nine experimentally characterized BGCs and their small molecule products, we identified gene gain/loss events, constrained interspecies recombination, and other evolutionary processes associated with vertical inheritance as major contributors to BGC diversification. These evolutionary dynamics had direct consequences for the compounds produced, as exemplified by species-level differences in salinosporamide production. Together, our results support the concept that specialized metabolites, and their cognate BGCs, can represent phylogenetically conserved functional traits with chemical diversification proceeding in species-specific patterns over evolutionary time frames. IMPORTANCE Microbial natural products are traditionally exploited for their pharmaceutical potential, yet our understanding of the evolutionary processes driving BGC evolution and compound diversification remain poorly developed. While HGT is recognized as an integral driver of BGC distributions, we find that the effects of vertical inheritance on BGC diversification had direct implications for species-level specialized metabolite production. As such, understanding the degree of genetic variation that corresponds to species delineations can enhance natural product discovery efforts. Resolving the evolutionary relationships between closely related strains and specialized metabolism can also facilitate our understanding of the ecological roles of small molecules in structuring the environmental distribution of microbes.
| S-EPMC8609351 | biostudies-literature
Project description:Systems-based characterization of specialized metabolites biosynthesis in Cornus officinalis
| PRJNA603009 | ENA
Project description:Filamentous fungi produce a vast array of secondary metabolites (SMs) and some of them are applied in agriculture or pharmacology. Recent sequencing of the rice pathogen Fusarium fujikuroi revealed the presence of far more SM-encoding genes than known products. SM production is energy-consuming and thus tightly regulated, leaving the majority of SM gene clusters silent under laboratory conditions. It is now well established that one important regulatory layer in SM biosynthesis involves histone modifications that render the genes either silent or poised for transcription. In this study, we show that the majority of the putative SM gene clusters in F. fujikuroi are located within facultative heterochromatin marked by H3K27me3. In this study, we performed comparative transcriptomics of a knock-down mutant of the responsible methyltransferase Kmt6 involved in H3K27 methylation grown on either solid complete medium or solid synthetic ICI medium. Overall four so far cryptic and otherwise silent putative SM gene clusters were significantly induced in the KMT6kd strain accompanied by reduced H3K27me3 levels at the respective gene loci and accumulation of novel metabolites. One of the four putative SM gene clusters, the STC5 gene cluster, was analysed in detail and heterologous expression of the key enzyme allowed for the identification of the first pathway-specific intermediate (1R,4R,5S)-guaia-6,10(14)-diene.
2016-07-04 | GSE80477 | GEO
Project description:Suppressing spurious cryptic transcription by a repressive intragenic chromatin state featuring trimethylated lysine 36 on histone H3 (H3K36me3) and DNA methylation is critical for maintaining self-renewal capacity in mouse embryonic stem cells. In yeast and nematodes, such cryptic transcription is elevated with age, and reducing the levels of age-associated cryptic transcription extends yeast lifespan. Whether cryptic transcription is also increased during mammalian aging is unknown. We show for the first time an age-associated elevation in cryptic transcription in several stem cell populations, including murine hematopoietic stem cells (mHSCs) and neuronal stem cells (NSCs) and human mesenchymal stem cells (hMSCs). Using DECAP-seq, we mapped and quantified age-associated cryptic transcription in hMSCs aged in vitro. Regions with significant age-associated cryptic transcription have a unique chromatin signature: decreased H3K36me3 and increased H3K4me1, H3K4me3, and H3K27ac with age. Furthermore, genomic regions undergoing such age-dependent chromatin changes resemble known promoter sequences and are bound by the promoter-associated protein TBP even in young cells. Hence, the more permissive chromatin state at intragenic cryptic promoters likely underlies the increase of cryptic transcription in aged mammalian stem cells.
2021-07-15 | GSE168063 | GEO
Project description:Glandular trichomes (GT) are specialized cell factories that have the capacity to produce large amounts of metabolites which can amount to over 10% of the leaf dry weight. The specific expression of secondary metabolite pathways in glandular trichomes has facilitated their elucidation. However, little is known about the connection between central carbon and specialized metabolism in these cells. To address this question, we used the type VI glandular trichomes from a cultivated (Solanum lycopersicum LA4024) and a wild tomato accession (Solanum habrochaites LA1777) as a model. Our study is based on metabolomics, transcriptomics, proteomics and 13C-labeling datasets of trichome and leaves samples. This comparative analysis allowed us to identify specific features of trichomes in comparison to leaves. Here, the transcript raw and RMA-normalized data is hosted.
2017-05-31 | E-MTAB-4482 | biostudies-arrayexpress
Project description:Suppressing spurious cryptic transcription by a repressive intragenic chromatin state featuring trimethylated lysine 36 on histone H3 (H3K36me3) and DNA methylation is critical for maintaining self-renewal capacity in mouse embryonic stem cells. In yeast and nematodes, such cryptic transcription is elevated with age, and reducing the levels of age-associated cryptic transcription extends yeast lifespan. Whether cryptic transcription is also increased during mammalian aging is unknown. We show for the first time an age-associated elevation in cryptic transcription in several stem cell populations, including murine hematopoietic stem cells (mHSCs) and neuronal stem cells (NSCs) and human mesenchymal stem cells (hMSCs). Using DECAP-seq, we mapped and quantified age-associated cryptic transcription in hMSCs aged in vitro. Regions with significant age-associated cryptic transcription have a unique chromatin signature: decreased H3K36me3 and increased H3K4me1, H3K4me3, and H3K27ac with age. Furthermore, genomic regions undergoing such age-dependent chromatin changes resemble known promoter sequences and are bound by the promoter-associated protein TBP even in young cells. Hence, the more permissive chromatin state at intragenic cryptic promoters likely underlies the increase of cryptic transcription in aged mammalian stem cells.
2021-07-15 | GSE156407 | GEO