Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Multilevel regulation of gene expression in brasilicardin biosynthetic gene cluster

ABSTRACT: Brasilicardin A, BraA, is a secondary metabolite produced by the bacterium Nocardia terpenica, and a promising drug due to potent immunosuppressive activity and low cytotoxicity. Currently, a semisynthetic approach confers production of a complete compound but suffers from insufficient biosynthesis of BraA intermediates used in the chemical synthesis steps leading to only lab scale quantities of the compound. A better understanding of gene expression regulatory pathways within the brasilicardin biosynthetic gene cluster, Bra-BGC, is a prerequisite to further improvements in the biosynthesis titers. However, a transcriptional regulation in Bra-BGC has only been superficially analyzed, till now. In this study, we comprehensively analyze the functions of several unstudied transcriptional regulators, KstR, SdpR and OmpR, encoded within the close vicinity of the Bra-BGC, and delve the role of the previously described cluster-situated activator Bra12. We present, that the Bra12 and the novel regulator SdpR, bind several DNA sequences located in the promoter regions of the genes essential for BraA biosynthesis. Subsequently, we demonstrate complex regulatory network through which both regulators are capable of controlling activity of those gene promoters and thus gene expression in Bra-BGC. Furthermore, using heterologous producer strain Amycolatopsis japonicum, we present, that Bra12 and SdpR regulators play opposite roles in brasilicardin congeners biosynthesis in. Finally, we propose a comprehensive model of multilevel gene expression regulation in Bra-BGC and propose the roles of locally encoded transcriptional regulators

ORGANISM(S): Nocardia terpenica

PROVIDER: GSE271981 | GEO | 2025/07/02

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Surges in biosynthetic gene cluster transcription are accompanied by bursts in natural compound production in the myxobacterium Sorangium sp. So ce836

Project description:An improved understanding of the genome-wide regulation of natural compound biosynthesis in bacterial producers may accelerate the discovery of novel biologically active molecules and facilitate their production. To this end, we have investigated the time course of genome-wide transcription in the myxobacterium Sorangium sp. So ce836 in relation to its production of natural compounds. Time-resolved RNA sequencing revealed the dynamic temporal variation of transcriptional activity, indicating that core biosynthesis genes from 48 biosynthetic gene clusters (BGCs; 92% of all BGCs encoded in the genome) were actively transcribed at specific time points in a batch culture. The majority (80%) of polyketide synthase and nonribosomal peptide synthetase genes displayed distinct peaks of transcription during exponential bacterial growth. Strikingly, these surges in BGC transcriptional activity were associated with boosts in the production of known natural compounds, indicating that their biosynthesis was crucially regulated at the transcriptional level. In contrast, BGC read counts from single time points had limited predictive value about biosynthetic activity, since transcription levels varied >100-fold among BGCs with detected natural products. Taken together, our time-course data provided unique insights into the dynamics of natural compound biosynthesis and its regulation in a wild-type myxobacterium, challenging the commonly cited notion of preferential BGC expression under meager conditions for bacterial growth. The close association between BGC transcription and compound production suggested that the molecular manipulation of transcriptional activity may be a viable strategy to increase compound yields from myxobacterial producer strains, warranting increased efforts to develop genetic engineering tools for these organisms.

2023-05-03 | GSE217497 | GEO

Brachyury controls Ciona notochord fate as part of a feedforward network [II]

Project description:The notochord is a defining feature of the chordates. The transcription factor Brachyury (Bra) is a key regulator of notochord fate but here we show that it is not a unitary master regulator in the model chordate Ciona. Ectopic Bra expression only partially reprograms other cell types to a notochord-like transcriptional profile and a subset of notochord-enriched genes are unaffected by CRISPR Bra disruption. We identify Foxa.a and Mnx as potential co-regulators and find that combinatorial cocktails are more effective at reprograming other cell types than Bra alone. We reassess the network relationships between Foxa.a, and other components of the notochord gene regulatory network and find that Foxa.a expression in the notochord is regulated by vegetal FGF signaling. It is a direct activator of Bra expression and has a binding motif that is significantly enriched in the regulatory regions of notochord-enriched genes. These and other results indicate that Bra and Foxa.a act together in a regulatory network dominated by positive feed-forward interactions, with neither being a classically-defined master regulator.er

2020-10-31 | GSE160545 | GEO

Brachyury controls Ciona notochord fate as part of a feedforward network [IV]

2020-10-31 | GSE160547 | GEO

Brachyury controls Ciona notochord fate as part of a feedforward network [III]

2020-10-31 | GSE160546 | GEO

Brachyury controls Ciona notochord fate as part of a feedforward network [I]

2020-10-31 | GSE160544 | GEO

Paleofuran BGC

Project description:Paleofuran BGC

| PRJEB75212 | ENA

Project description:Accramycin BGC

| PRJNA560219 | ENA

Homo sapiens

Project description:Regulators of Human Androgen Biosynthesis

| PRJNA348635 | ENA

Discovery of a novel antifungal compound, ilicicolin K, through genetic activation of the ilicicolin biosynthetic pathway in Trichoderma reesei

Project description:In the quest to discover novel antifungal agents and new antifungal production processes, we investigated the biosynthetic gene cluster (BGC) for ilicicolin H in the fungus Trichoderma reesei. While the BGC is silent under standard cultivation conditions, we achieved to activate it by over-expressing its transcription factor TriliR. Successful BGC activation was confirmed by RT-qPCR, proteomic and metabolomic analyses. Metabolomic profiling upon BGC expression revealed high-yield production of the supposed main product ilicicolin H. To elucidate the functionality of this BGC, we employed a combination of overexpression and deletions of individual biosynthetic gene cluster constituents. Deletion of triliA, encoding for the core polyketide synthase TriliA, completely ceased product formation, as expected. In contrast to previous heterologous expression experiments, we could demonstrate that the epimerase TriliE is necessary for the formation of ilicicolin H in the native host. While we hardly observed any of the previously reported side- or shunt products associated with heterologous ilicicolin H expression, we discovered a novel member of the ilicicolin family using a metabolomic molecular networking approach. This new compound, which we termed ilicicolin K, is expressed in substantial amounts in the genetically engineered Trichoderma reesei, enabling us to elucidate its structure by NMR. The structure of ilicicolin K is similar to that of ilicicolin H but differs by an additional hydroxylation and an intramolecular etherification of the hydroxyl group at the pyridone towards the tyrosine moiety of the molecule. Initial tests of ilicicolin K showed antifungal activity against Saccharomyces cerevisiae and Aspergillus nidulans with a similar minimum inhibitory concentration as ilicicolin H.

2025-03-13 | PXD055742 | Pride

BRACHYURY orchestrates distinct mesoderm and endoderm gene regulatory networks in differentiating human embryonic stem cells

Project description:The transcription factor BRACHYURY (T, BRA) is one of the first markers of gastrulation and lineage specification in mammals. Despite its wide use and importance in stem cell and developmental biology, its genomic targets are largely unknown. Here, we used differentiated human embryonic stem cells to study the role of BRA in Bmp4-induced mesoderm and Activin-induced endoderm progenitors by ChIP-seq. We show that BRA has distinct genome-wide binding landscapes in these two populations. Our data illuminate the function of BRA in the context of human embryonic development and show that the regulatory role of BRA is context-dependent.

2015-05-18 | GSE60606 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data