Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

The natural product co-evolved pyrroloquinoline quinone operon enhances their production when heterologously expressed in a variety of Streptomycetes

ABSTRACT: Streptomyces has the largest repertoire of natural product biosynthetic gene clusters (BGCs), yet developing a universal engineering strategy for each Streptomyces species is challenging. Given that some Streptomyces species have larger BGC repertoires than others, we hypothesized that a set of genes co-evolved with BGCs to support biosynthetic proficiency must exist in those strains, and that their identification may provide universal strategies to improve the productivity of other strains. We show here that genes co-evolved with natural product BGCs in Streptomyces can be identified by phylogenomics analysis. Among the 597 genes that co-evolved with polyketide BGCs, 11 genes in the “coenzyme” category have been examined, including a gene cluster encoding for the co-factor pyrroloquinoline quinone (PQQ). When the pqq gene cluster was engineered into 11 Streptomyces strains, it enhanced production of 16,385 metabolites, including 36 known natural products with up to 40-fold improvement and several activated silent gene clusters. This study provides a new engineering strategy for improving polyketide production and discovering new biosynthetic gene clusters.

ORGANISM(S): Streptomyces Coelicolor A3(2)

SUBMITTER: Xiaozhou Luo

PROVIDER: PXD049454 | iProX | Mon Feb 12 00:00:00 GMT 2024

REPOSITORIES: iProX

ACCESS DATA

Json Xml

Similar Datasets

The natural product co-evolved pyrroloquinoline quinone operon enhances their production when heterologously expressed in a variety of Streptomycetes

Project description:Streptomyces has the largest repertoire of natural product biosynthetic gene clusters (BGCs), yet developing a universal engineering strategy for each Streptomyces species is challenging. Given that some Streptomyces species have larger BGC repertoires than others, we hypothesized that a set of genes co-evolved with BGCs to support biosynthetic proficiency must exist in those strains, and that their identification may provide universal strategies to improve the productivity of other strains. We show here that genes co-evolved with natural product BGCs in Streptomyces can be identified by phylogenomics analysis. Among the 597 genes that co-evolved with polyketide BGCs, 11 genes in the “coenzyme” category have been examined, including a gene cluster encoding for the co-factor pyrroloquinoline quinone (PQQ). When the pqq gene cluster was engineered into 11 Streptomyces strains, it enhanced production of 16,385 metabolites, including 36 known natural products with up to 40-fold improvement and several activated silent gene clusters. This study provides a new engineering strategy for improving polyketide production and discovering new biosynthetic gene clusters.

2024-03-01 | GSE256209 | GEO

Project description:Evaluating Distribution of Bacterial Natural Product Biosynthetic Gene Clusters Across Lake Huron Sediment

| PRJNA690811 | ENA

Production of chain-extended cinnamoyl compounds by overexpressing two adjacent cluster-situated LuxR regulators in Streptomyces globisporus C-1027

Project description:Natural products from microorganisms are important sources for drug discovery. With the development of high-throughput sequencing technology and bioinformatics, a large amount of uncharacterized biosynthetic gene clusters (BGCs) in microorganisms have been found, which show the potential for novel natural product production. 9 BGCs containing PKS and/or NRPS in Streptomyces globisporus C-1027 were transcriptionally low/silent under the experimental fermentation conditions, and the products of these clusters are unknown. Thus, we tried to activate these BGCs to explore cryptic products of this strain. We constructed the cluster-situated regulator overexpressing strains which contained regulator gene(s) under the control of the constitutive promoter ermE*p in S. globisporus C-1027. Overexpression of regulators in cluster 26 resulted in significant transcriptional upregulation of biosynthetic genes. With the separation and identification of products from the overexpressing strain OELuxR1R2, 3 ortho-methyl phenyl alkenoic acids (compounds 1-3) were obtained. Gene disruption showed that compounds 1 and 2 were completely abolished in the mutant GlaEKO, but were hardly affected by deletion of the genes orf3 or echA in cluster 26. The type II PKS biosynthetic pathway of chain-extended cinnamoyl compounds was deduced by bioinformatics analysis. This study showed that overexpression of the 2 adjacent cluster-situated LuxR regulator(s) is an effective strategy to connect the orphan BGC to its products.

2023-09-06 | MTBLS5152 | MetaboLights

Nassar2022 - Biosynthetic Gene Cluster (BGC) products NER model

Project description:bgc-gene-product model is a Named Entity Recognition (NER) model that identifies and annotates the protein products of Biosynthetic Gene Clusters (BGCs) in texts.

2022-03-10 | MODEL2203040006 | BioModels

Nassar2022 - Biosynthetic Gene Cluster (BGC) genes NER model

Project description:bgc-gene-name model is a Named Entity Recognition (NER) model that identifies and annotates the genes of Biosynthetic Gene Clusters (BGCs) in texts.

2022-03-10 | MODEL2203040005 | BioModels

RNA-Sequenzing of Streptomyces coelicolor A3(2) (M1152) in timeseries

Project description:SYSTERACT: Systematic Rebuilding of Actinomycetes for Natural Product Formation For several decades antibiotics have saved millions of lives, but their overuse makes them less effective due to increase in bacterial resistance. Because of this major clinical and public health problem, there is an urgent need for new effective antimicrobials. The ERASysAPP project SYSTERACT aims to further develop, the model actinobacterium Streptomyces coelicolor into improved microbial cell factories to heterologously produce diverse bioactive compounds in amounts needed for structural and functional evaluation. Unprecedented systems biology understanding of S. coelicolor is being combined with morphology engineering and improved (de-)regulation and precursor supply to accelerate bioactive compound discovery efforts. By that means, we aim to generate a stepwise improved 'Superhost' for the production of antibiotics in which metabolic bottlenecks and regulatory restriction are greatly mitigated. The optimized strains will be tested concerning their applicability for an improved production of commercially relevant antibiotics and the expression of novel bioactive gene clusters identified in new actinomycete strains and environmental metagenomes. So far two strains, M145 and M1152, have been cultivated for time-resolved 'omics sampling, and a larger number of additional strains are on the list for similar experiments. High quality RNAseq-based transcriptome data have been generated and processed. M145 is the wildtype strain in S. coelicolor (as used in STREAM, see also GSE18489), 3 biol. replicas and M1152 lacks four major biosynthetic gene clusters, undecylprodigine (RED), calcium-dependent antibiotic (CDA), coelimycin (CPK) and actinorhodin (ACT). Contributors: A. Wentzel, W. Wohlleben, G. van Wezel, D van Dissel, O. Wolkenhauer, E. Kerkhoven, N. Spidsoe, K. Nieselt and the SYSTERACT consortium

2019-10-09 | GSE132488 | GEO

RNA-Sequencing of Streptomyces coelicolor A3(2) (M145) in timeseries

2019-10-09 | GSE132487 | GEO

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

Adrenaline-mediated activation of antibiotic production in Streptomyces highlights catechol as elicitor of specialized metabolism

Project description:Actinobacteria are a rich source of bioactive molecules, and genome sequencing has shown that the vast majority of their biosynthetic potential has yet to be explored. However, many of their biosynthetic gene clusters (BGCs) are poorly expressed in the laboratory, which prevents discovery of their cognate natural products. To exploit their full biosynthetic potential, better understanding of the signals that promote the expression of BGCs is needed. Here, we show that the human stress hormone epinephrine (adrenaline) elicits antibiotic production by Actinobacteria. Catechol was established as the likely eliciting moiety, since similar responses were seen for catechol and for the catechol-containing molecules dopamine and catechin but not for related molecules. Exploration of the catechol-responsive strain Streptomyces sp. MBT84 using mass spectral networking revealed elicitation of a BGC that produces the angucycline glycosides aquayamycin, urdamycinone B and galtamycin C. Heterologous expression of the catechol-cleaving enzymes catechol 1,2-dioxygenase or catechol 2,3 dioxygenase counteracted the eliciting effect of catechol. Thus, for the first time we show the activation of natural product biosynthesis by a human hormone, leading to the identification of the ubiquitous catechol moiety as elicitor of BGCs for siderophores and antibiotics.

2022-01-10 | PXD030484 | Pride

Adrenaline-mediated activation of antibiotic production in Streptomyces highlights catechol as elicitor of specialized metabolism

2022-02-04 | PXD030319 | Pride

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

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