Discovery of lydiamycin A biosynthetic gene cluster in the plant pathogen Rhodococcus fascians guides structural revision and identification of molecular target
Ontology highlight
ABSTRACT:
INSTRUMENT(S): Q Exactive
ORGANISM(S): Rhodococcus Fascians (ncbitaxon:1828)
SUBMITTER: 
Andrew Truman
PROVIDER: MSV000097741 | MassIVE | Sun Apr 27 14:30:00 BST 2025
REPOSITORIES: MassIVE
Similar Datasets
Project description:We report ATAC-seq for several A. thaliana accessions in healthy leaf tissue. As part of an investigation into the evolution of conserved noncoding sequences, our goal was to identify overlaps between regions of accessible chromatin and CNS. Manuscript in review. Biorxiv preprint doi: https://doi.org/10.1101/727669
2021-01-04 | GSE164159 | GEO
Project description:WDR5 inhibitors have been implicated as a therapeutic vulnerability in glioblastoma cancer stem cells (CSCs). We tested the transcriptional effects of two different WDR5 WIN-site inhibitors, the dihydroisoquinoline C16 and the triazole C3TD078, in two CSC models (L0 and DI318) by bulk RNAseq.These data are associated with Coker et al., "Development and Characterization of Triazole-Based WDR5 Inhibitors for the Treatment of Glioblastoma," bioRxiv, 2025, https://doi.org/10.1101/2025.07.29.667410.
2025-08-15 | GSE304999 | GEO
Project description:Recent reports have revealed genomic clustering of enzymatic genes for particular biosynthetic pathways in plant specialized/secondary metabolism. Rice (Oryza sativa) carries two such clusters for production of antimicrobial diterpenoid phytoalexins, with the cluster on chromosome 2 containing four closely related/homologous members of the cytochrome P450 CYP76M subfamily (CYP76M5-8). Notably, the underlying evolutionary expansion of these CYP appears to have occurred after assembly of the ancestral biosynthetic gene cluster, suggesting separate roles. It has been demonstrated that CYP76M7 catalyzes C11α-hydroxylation of ent-cassadiene, and presumably mediates an early step in biosynthesis of the derived phytocassane class of phytoalexins. Here we report biochemical characterization of CYP76M5, -6, and -8. Our results indicate that CYP76M8 is a multifunctional/promiscuous hydroxylase, with CYP76M5 and -7 seeming to provide only redundant activity, while CYP76M6 seems to provide both redundant and novel activity, relative to CYP76M8. RNAi-mediated double knockdown of CYP76M7 and -8 suppresses elicitor inducible phytocassane production, indicating a role for these monooxygenases in phytocassane biosynthesis. In addition, our data suggests that CYP76M5, -6, and -8 may play redundant roles in production of the oryzalexin class of phytoalexins as well. Intriguingly, the preceding diterpene synthase for oryzalexin biosynthesis, unlike that for the phytocassanes, is not found in the chromosome 2 diterpenoid biosynthetic gene cluster. Accordingly, our results not only uncover a complex evolutionary history, but also further suggest some intriguing differences between plant biosynthetic gene clusters and the seemingly similar microbial operons. The implications for the underlying metabolic evolution of plants are then discussed.
| S-EPMC3307284 | biostudies-literature
Project description:This dataset contains single cell RNAseq of human iPSCs undergoing cytokine-mediated differentiation alongside targeted CRISPR-mediated endogenous gene activation. For this experiment we sequenced single cells at day 10 of the differentiation protocol, when the cells undergo the endothelial-to-hematopoietic transition described in the paper Petazzi et al, BiorXiv DOI 10.1101/2022.10.04.510611 The dataset contains four libraries: (1) iSAM line infected with non-targeting guide RNA, (2) iSAM line infected with non-targeting guide RNA treated with Dox, (3) iSAM line infected with targeting guide RNAs library, (4) iSAM line infected with targeting guide RNAs library treated with Dox
2024-03-21 | E-MTAB-12748 | biostudies-arrayexpress
Project description:Two phenazine compounds, diastaphenazine and izumiphenazine C, with complex structures and promising antitumour activity have been isolated from the plant endophytic actinomycete Streptomyces diastaticus W2. Their putative biosynthetic gene cluster (dap) was identified by heterologous expression and gene knockout. There are twenty genes in the dap cluster. dap14-19 related to shikimic pathway were potentially involved in the precursor chorismic acid biosynthesis, and dapBCDEFG were confirmed to be responsible for the biosynthesis of the dibenzopyrazine ring, the nuclear structure of phenazines. Two transcriptional regulatory genes dapR and dap4 played the positive regulatory roles on the phenazine biosynthetic pathway. Most notably, the dimerization of the dibenzopyrazine ring in diastaphenazine and the loading of the complex side chain in izumiphenazine C could be catalysed by the cyclase homologous gene dap5, suggesting an unusual modification strategy tailoring complex phenazine biosynthesis. Moreover, metabolite analysis of the gene deletion mutant strain S. albus::23C5Δdap2 and substrate assay of the methyltransferase Dap2 clearly revealed the biosynthetic route of the complex side chain in izumiphenazine C.
| S-EPMC8966011 | biostudies-literature
Project description:The Pc locus of sorghum (Sorghum bicolor) determines dominant sensitivity to a host-selective toxin produced by the fungal pathogen Periconia circinata. The Pc region was cloned by a map-based approach and found to contain three tandemly repeated genes with the structures of nucleotide binding site-leucine-rich repeat (NBS-LRR) disease resistance genes. Thirteen independent Pc-to-pc mutations were analyzed, and each was found to remove all or part of the central gene of the threesome. Hence, this central gene is Pc. Most Pc-to-pc mutations were associated with unequal recombination. Eight recombination events were localized to different sites in a 560-bp region within the approximately 3.7-kb NBS-LRR genes. Because any unequal recombination located within the flanking NBS-LRR genes would have removed Pc, the clustering of cross-over events within a 560-bp segment indicates that a site-directed recombination process exists that specifically targets unequal events to generate LRR diversity in NBS-LRR loci.
| S-EPMC2593579 | biostudies-literature
Project description:The biosynthetic gene cluster of porothramycin, a sequence-selective DNA alkylating compound, was identified in the genome of producing strain Streptomyces albus subsp. albus (ATCC 39897) and sequentially characterized. A 39.7 kb long DNA region contains 27 putative genes, 18 of them revealing high similarity with homologous genes from biosynthetic gene cluster of closely related pyrrolobenzodiazepine (PBD) compound anthramycin. However, considering the structures of both compounds, the number of differences in the gene composition of compared biosynthetic gene clusters was unexpectedly high, indicating participation of alternative enzymes in biosynthesis of both porothramycin precursors, anthranilate, and branched L-proline derivative. Based on the sequence analysis of putative NRPS modules Por20 and Por21, we suppose that in porothramycin biosynthesis, the methylation of anthranilate unit occurs prior to the condensation reaction, while modifications of branched proline derivative, oxidation, and dimethylation of the side chain occur on already condensed PBD core. Corresponding two specific methyltransferase encoding genes por26 and por25 were identified in the porothramycin gene cluster. Surprisingly, also methyltransferase gene por18 homologous to orf19 from anthramycin biosynthesis was detected in porothramycin gene cluster even though the appropriate biosynthetic step is missing, as suggested by ultra high-performance liquid chromatography-diode array detection-mass spectrometry (UHPLC-DAD-MS) analysis of the product in the S. albus culture broth.
| S-EPMC4194701 | biostudies-literature
Project description: Not available
| S-EPMC5714517 | biostudies-literature
Project description:Members of the diazaquinomycin class of natural products have shown potent and selective activity against Mycobacterium tuberculosis. However, poor aqueous solubility has prevented extensive studies in animal models thus far. Our long-term goal is to harness knowledge regarding diazaquinomycin biosynthesis towards the generation of derivatives for structure-activity relationship studies. We have previously sequenced the genomes of two diazaquinomycin-producing, actinomycete bacteria and identified putative daq biosynthetic gene clusters. Here, we report the heterologous expression of the daq gene cluster from the marine Streptomyces sp. F001 in S. coelicolor M1152. In addition to serving as functional proof for gene cluster assignment, the heterologous expression system reported here is expected to facilitate investigations aimed at elucidating diazaquinomycin biosynthesis.
| S-EPMC6801048 | biostudies-literature
Project description:Computational analysis of biosynthetic gene clusters (BGCs) has revolutionized natural product discovery by enabling the rapid investigation of secondary metabolic potential within microbial genome sequences. Grouping homologous BGCs into Gene Cluster Families (GCFs) facilitates mapping their architectural and taxonomic diversity and provides insights into the novelty of putative BGCs, through dereplication with BGCs of known function. While multiple databases exist for exploring BGCs from publicly available data, no public resources exist that focus on GCF relationships. Here, we present BiG-FAM, a database of 29,955 GCFs capturing the global diversity of 1,225,071 BGCs predicted from 209,206 publicly available microbial genomes and metagenome-assembled genomes (MAGs). The database offers rich functionalities, such as multi-criterion GCF searches, direct links to BGC databases such as antiSMASH-DB, and rapid GCF annotation of user-supplied BGCs from antiSMASH results. BiG-FAM can be accessed online at https://bigfam.bioinformatics.nl.
| S-EPMC7778980 | biostudies-literature