Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

INLP discovery from M. fortuitum culture extracts

ABSTRACT: The dataset contains untargeted metabolomic data from Mycobacterium fortuitum wild-type culture extracts and INLP biosynthetic gene cluster (BGC) knockout strains, enabling comparative metabolomic analysis and precursor neutral-loss chromatography (pNLC) based annotation. MS/MS spectra for compound 3 (fortcupinile A) and compound 4 (fortlipoamide A) are also included.

INSTRUMENT(S): 6545 Q-TOF LC/MS

ORGANISM(S): Mycobacterium Fortuitum

SUBMITTER: Wenjun Zhang

PROVIDER: MSV000098566 | MassIVE | Sat Jul 19 21:44:00 BST 2025

REPOSITORIES: MassIVE

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

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

Multilevel regulation of gene expression in brasilicardin biosynthetic gene cluster

Project description: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

2025-07-02 | GSE271981 | 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

Nassar2022 - Biosynthetic Gene Cluster (BGC) compound NER model

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

2022-03-10 | MODEL2203040004 | BioModels

GNPS Maculalactone BGC transformed in Ecoli

Project description:This dataset includes samples of the Maculalctone biosynthetic gene cluster (mac BGC) captured in Nodularia sp. NIES-3585 and heterologously expressed in E. coli. Total = complete BGC CDEF = minimal BGC Empty vector = control

2025-02-07 | MSV000097078 | GNPS

Biosynthetic Gene Cluster regulatory sequence library profiled in S. albidoflavus

Project description:Here, we profiled the transcriptional capacity of a library of regulatory sequences mined from diverse Biosynthetic Gene Clusters in S. albidoflavus (S. albus J1074) to investigate BGC gene regulation.

2022-06-07 | E-MTAB-9223 | biostudies-arrayexpress

Elucidation of genes enhancing natural product biosynthesis through co-evolution analysis

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

Biosynthesis of Isonitrile Lipopeptides by Conserved Non-ribosomal Peptide Synthetase Gene Clusters in Actinobacteria

Project description:A putative lipopeptide biosynthetic gene cluster is conserved in many species of Actinobacteria, including Mycobacterium tuberculosis and Mycobacterium marinum, but the specific function of the encoding proteins has been elusive. Using both in vivo heterologous reconstitution and in vitro biochemical analyses, we have revealed that the five encoding biosynthetic enzymes are capable of synthesizing a new family of isonitrile lipopeptides (INLPs) through a thio-template mechanism. The biosynthesis features the generation of isonitrile from a single precursor Gly promoted by a thioesterase and a non-heme iron(II)-dependent oxidase homologue, and the acylation of both amino groups of Lys by the same isonitrile acyl chain facilitated by a single condensation domain of a non-ribosomal peptide synthetase (NRPS). In addition, the deletion of INLP biosynthetic genes in M. marinum has decreased the intracellular metal concentration, suggesting the role of this biosynthetic gene cluster in metal transport.

2017-07-18 | MTBLS454 | MetaboLights

Streptomyces sp. SCSIO ZS0520

Project description:Actinopyrone biosynthetic gene cluster

| PRJNA778327 | ENA

Streptomyces albidoflavus

Project description:cyclofaulknamycin biosynthetic gene cluster

| PRJDB18021 | ENA