Similar Datasets
Project description:Specialized biosynthetic gene clusters in Streptomyces are subject to complex regulation involving both transcriptional control and chromosome organization. The nucleoid-associated protein Lsr2 silences many of these clusters, yet how it shapes the global chromatin structure and how its conserved paralog LsrL contributes to this process remain poorly understood. In this study, we applied a multi-omics approach, combining transcriptional activity, genome-wide protein-DNA binding profiles, and three-dimensional chromosome conformation to characterize the coordination of Lsr2 and LsrL in exerting transcriptional control and genome architecture in Streptomyces venezuelae. In line with established Lsr2 functions, we find that Lsr2 sets broad transcriptional boundaries, while LsrL acts in a more context-specific manner that depends on the presence of Lsr2 and may function to reinforce or modulate Lsr2-mediated silencing. Loss of Lsr2 reshaped the chromatin landscape genome-wide, relieving its restriction on short-range contacts, triggering strong transcriptional changes and new domain boundaries near de-repressed BGCs. These findings establish Lsr2 as a dominant but contextually modulated regulator whose interplay with LsrL coordinates specialized metabolism with higher-order chromosome organization.
2026-02-11 | GSE310104 | GEO
Project description:Specialized biosynthetic gene clusters in Streptomyces are subject to complex regulation involving both transcriptional control and chromosome organization. The nucleoid-associated protein Lsr2 silences many of these clusters, yet how it shapes the global chromatin structure and how its conserved paralog LsrL contributes to this process remain poorly understood. In this study, we applied a multi-omics approach, combining transcriptional activity, genome-wide protein-DNA binding profiles, and three-dimensional chromosome conformation to characterize the coordination of Lsr2 and LsrL in exerting transcriptional control and genome architecture in Streptomyces venezuelae. In line with established Lsr2 functions, we find that Lsr2 sets broad transcriptional boundaries, while LsrL acts in a more context-specific manner that depends on the presence of Lsr2 and may function to reinforce or modulate Lsr2-mediated silencing. Loss of Lsr2 reshaped the chromatin landscape genome-wide, relieving its restriction on short-range contacts, triggering strong transcriptional changes and new domain boundaries near de-repressed BGCs. These findings establish Lsr2 as a dominant but contextually modulated regulator whose interplay with LsrL coordinates specialized metabolism with higher-order chromosome organization.
2026-02-11 | GSE310101 | GEO
Project description:Specialized biosynthetic gene clusters in Streptomyces are subject to complex regulation involving both transcriptional control and chromosome organization. The nucleoid-associated protein Lsr2 silences many of these clusters, yet how it shapes the global chromatin structure and how its conserved paralog LsrL contributes to this process remain poorly understood. In this study, we applied a multi-omics approach, combining transcriptional activity, genome-wide protein-DNA binding profiles, and three-dimensional chromosome conformation to characterize the coordination of Lsr2 and LsrL in exerting transcriptional control and genome architecture in Streptomyces venezuelae. In line with established Lsr2 functions, we find that Lsr2 sets broad transcriptional boundaries, while LsrL acts in a more context-specific manner that depends on the presence of Lsr2 and may function to reinforce or modulate Lsr2-mediated silencing. Loss of Lsr2 reshaped the chromatin landscape genome-wide, relieving its restriction on short-range contacts, triggering strong transcriptional changes and new domain boundaries near de-repressed BGCs. These findings establish Lsr2 as a dominant but contextually modulated regulator whose interplay with LsrL coordinates specialized metabolism with higher-order chromosome organization.
2026-02-11 | GSE310097 | GEO
Project description:The goal of this work was to determine where Lsr2 binds within the S. venezuelae chromosome, and to differentiate between direct versus indirect effects by comparing our ChIP-seq results with RNA-seq results
2018-06-09 | GSE115538 | GEO
Project description:Comparative transcriptional profiling of a ΔbldM mutant of Streptomyces venezuelae with its unmodified progenitor revealed that the expression of a cryptic biosynthetic gene cluster containing both type I and type III polyketide synthase genes is activated in the mutant. The 29.5 kb gene cluster, which was predicted to encode an unusual biaryl metabolite, which we named venemycin, and potentially halogenated derivatives, contains 16 genes including one-vemR-that encodes a transcriptional activator of the large ATP-binding LuxR-like (LAL) family. Constitutive expression of vemR in the ΔbldM mutant led to the production of sufficient venemycin for structural characterisation, confirming its unusual biaryl structure. Co-expression of the venemycin biosynthetic gene cluster and vemR in the heterologous host Streptomyces coelicolor also resulted in venemycin production. Although the gene cluster encodes two halogenases and a flavin reductase, constitutive expression of all three genes led to the accumulation only of a monohalogenated venemycin derivative, both in the native producer and the heterologous host. A competition experiment in which equimolar quantities of sodium chloride and sodium bromide were fed to the venemycin-producing strains resulted in the preferential incorporation of bromine, thus suggesting that bromide is the preferred substrate for one or both halogenases.
| S-EPMC5132015 | biostudies-literature
Project description:Streptomyces species have attracted considerable interest as a reservoir of medically important secondary metabolites, which are even diverse and different between strains. Here, we reassess ten Streptomyces venezuelae strains by presenting the highly resolved classification, using 16S rRNA sequencing, MALDI-TOF MS protein profiling, and whole-genome sequencing. The results revealed that seven of the ten strains were misclassified as S. venezuelae species. Secondary metabolite biosynthetic gene cluster (smBGC) mining and targeted LC-MS/MS based metabolite screening of S. venezuelae and misclassified strains identified in total 59 secondary metabolites production. In addition, a comparison of pyrrolamide-type antibiotic BGCs of four misclassified strains, followed by functional genomics, revealed that athv28 is critical in the synthesis of the anthelvencin precursor, 5-amino-3,4-dihydro-2H-pyrrole-2-carboxylate (ADPC). Our findings illustrate the importance of the accurate classification and better utilization of misclassified Streptomyces strains to discover smBGCs and their secondary metabolite products.
| S-EPMC8627960 | biostudies-literature
Project description:JadL was identified as a Major Facilitator Superfamily (MFS) transporter (T.C. 2.A.1) through sequence homology. The protein is encoded by jadL, situated within the jadomycin biosynthetic gene cluster. JadL has, therefore, been assigned a putative role in host defense by exporting its probable substrates, the jadomycins, a family of secondary metabolites produced by Streptomyces venezuelae ISP5230. Herein, we evaluate this assumption through the construction and analysis of a jadL disrupted mutant, S. venezuelae VS678 (ΔjadL::aac(3)IV). Quantitative determination of jadomycin production with the jadL disrupted mutant did not show a significant decrease in production in comparison to the wildtype strain, as determined by HPLC and by tandem mass spectrometry. These results suggest that efflux of jadomycin occurs upon disruption of jadL, or that JadL is not involved in jadomycin efflux. Potentially, other transporters within S. venezuelae ISP5230 may adopt this role upon inactivation of JadL to export jadomycins.
| S-EPMC5359229 | biostudies-literature
Project description:This SuperSeries is composed of the SubSeries listed below.
2018-06-09 | GSE115439 | GEO
Project description:Doxorubicin, one of the most widely used anticancer drugs, is composed of a tetracyclic polyketide aglycone and l-daunosamine as a deoxysugar moiety, which acts as an important determinant of its biological activity. This is exemplified by the fewer side effects of semisynthetic epirubicin (4'-epi-doxorubicin). An efficient combinatorial biosynthetic system that can convert the exogenous aglycone ?-rhodomycinone into diverse glycosylated derivatives of doxorubicin or its biosynthetic intermediates, rhodomycin D and daunorubicin, was developed through the use of Streptomyces venezuelae mutants carrying plasmids that direct the biosynthesis of different nucleotide deoxysugars and their transfer onto aglycone, as well as the postglycosylation modifications. This system improved epirubicin production from ?-rhodomycinone by selecting a substrate flexible glycosyltransferase, AknS, which was able to transfer the unnatural sugar donors and a TDP-4-ketohexose reductase, AvrE, which efficiently supported the biosynthesis of TDP-4-epi-l-daunosamine. Furthermore, a range of doxorubicin analogs containing diverse deoxysugar moieties, seven of which are novel rhodomycin D derivatives, were generated. This provides new insights into the functions of deoxysugar biosynthetic enzymes and demonstrates the potential of the S. venezuelae-based combinatorial biosynthetic system as a simple biological tool for modifying structurally complex sugar moieties attached to anthracyclines as an alternative to chemical syntheses for improving anticancer agents.
| S-EPMC3147398 | biostudies-literature
Project description:In a survey of microbial systems capable of generating unusual metabolite structural variability, Streptomyces venezuelae ATCC 15439 is notable in its ability to produce two distinct groups of macrolide antibiotics. Methymycin and neomethymycin are derived from the 12-membered ring macrolactone 10-deoxymethynolide, whereas narbomycin and pikromycin are derived from the 14-membered ring macrolactone, narbonolide. This report describes the cloning and characterization of the biosynthetic gene cluster for these antibiotics. Central to the cluster is a polyketide synthase locus (pikA) that encodes a six-module system comprised of four multifunctional proteins, in addition to a type II thioesterase (TEII). Immediately downstream is a set of genes for desosamine biosynthesis (des) and macrolide ring hydroxylation. The study suggests that Pik TEII plays a role in forming a metabolic branch through which polyketides of different chain length are generated, and the glycosyl transferase (encoded by desVII) has the ability to catalyze glycosylation of both the 12- and 14-membered ring macrolactones. Moreover, the pikC-encoded P450 hydroxylase provides yet another layer of structural variability by introducing regiochemical diversity into the macrolide ring systems. The data support the notion that the architecture of the pik gene cluster as well as the unusual substrate specificity of particular enzymes contributes to its ability to generate four macrolide antibiotics.
| S-EPMC22793 | biostudies-literature