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Discovery and characterization of the first known biological lanthanide chelator

ABSTRACT: Discovery and characterization of the first known biological lanthanide chelator

PROVIDER: PRJNA1021179 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR26182984_1.fastq.gz	Fastqsanger.gz
	SRR26182984_2.fastq.gz	Fastqsanger.gz
	SRR26182985_1.fastq.gz	Fastqsanger.gz
	SRR26182985_2.fastq.gz	Fastqsanger.gz
	SRR26182986_1.fastq.gz	Fastqsanger.gz

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Discovery and characterization of the first known biological lanthanide chelator

Project description:Many bacteria secrete metallophores, low-molecular weight organic compounds that bind ions with high selectivity and affinity, in order to access essential metals from the environment. The biosynthetic machinery to produce metallophores as well as their structures have been elucidated for iron, zinc, nickel, molybdenum, and copper specific molecules. No lanthanide-specific metallophore has been discovered despite the knowledge that lanthanide metals (Ln) have recently been revealed to be essential cofactors for certain alcohol dehydrogenases across a diverse range of phyla. Here, we report the biosynthetic machinery for, the structure of, and the physiological relevance of the first known lanthanophore, methylolanthanin. The structure of methylolanthanin exhibits a unique 4-hydroxybenzoate moiety which has not previously been described in other metallophores. We find that production of methylolanthanin is required for normal levels of Ln accumulation in the methylotrophic bacterium Methylobacterium extorquens AM1, while overexpression of the molecule greatly increases bioaccumulation. Our results provide a clearer understanding of how Ln-utilizing bacteria sense, scavenge, and store Ln; essential processes in the environment where Ln are poorly bioavailable. Beyond Ln, we anticipate our study to be a starting point for understanding how organisms acquire other f-block metals, the actinides. More broadly, the discovery of a lanthanophore opens doors for study of how biosynthetic gene clusters are repurposed for new functions, how metallophores acquire their metal specificity, and the complex relationship between metal homeostasis and fitness.

2023-10-16 | GSE244060 | GEO

Lanthanide response of the obligate methylotroph Methylobacillus flagellatus and discovery of lanpepsy, a novel lanthanide-binding protein

Project description:Lanthanides were recently discovered as metals required in the active site of certain methanol dehydrogenases. Since then, the characterization of the lanthanome, i.e. all proteins involved in sensing, uptake, and utilization of lanthanides, has become an active field of research. Initial exploration of the response to lanthanides in methylotrophs has revealed that the lanthanome is not conserved and that multiple mechanisms for lanthanide utilization must exist. Here we investigated the lanthanome in the obligate model methylotroph Methylobacillus flagellatus. We used a proteomic approach to analyze differentially regulated proteins in the presence of lanthanum. While multiple known proteins showed induction upon growth in presence of lanthanum (Xox proteins, TonB-dependent receptor), we also identified several novel proteins not previously associated with lanthanide utilization. Among these was Mfla_0908, a periplasmic 19 kDa-protein without functional annotation. The protein comprises two characteristic PepSY domains and we thus termed the protein lanpepsy (LanP). Based on bioinformatic analysis, we speculated that LanP could be involved in lanthanide binding. Using dye competition assays as well as protein ultrafiltration followed by inductively coupled plasma mass spectrometric analysis, we demonstrated the presence of four lanthanide binding sites that showed selectivity over the chemically similar Ca2+ ion. A similar arrangement of two PepSY domains is also present in the recently described uranium-binding protein UipA from Microbacterium spp. LanP and UipA thus represent the first members of PepSY domain proteins involved in metal binding. Although the physiological role of LanP is still unclear, its discovery has important implications for applications towards the sustainable purification and separation of lanthanides.

2023-01-31 | PXD032828 | Pride

A mutagenic screen identifies a TonB-dependent receptor required for the lanthanide metal switch in the Type I methanotroph “Methylotuvimicrobium buryatense” 5GB1C

Project description:Several of the metabolic enzymes in methanotrophic bacteria rely on metals for both their expression and their catalysis. The MxaFI methanol dehydrogenase enzyme complex uses calcium as a cofactor to oxidize methanol, while the alternative methanol dehydrogenase XoxF uses lanthanide metals such as lanthanum and cerium for the same function. Lanthanide metals, abundant in the earth’s crust and widely used in electronic devices, strongly repress the transcription of mxaF yet activate the transcription of xoxF. This phenomenon of mxaF repression and xoxF activation in the presence of lanthanides is called the “lanthanide switch.” To better understand components of the lanthanide switch in the Type I gammaproteobacterial methanotroph “Methylotuvimicrobium buryatense” 5GB1C, we designed a mutagenesis system and selected for mutants unable to repress the mxaF promoter in the presence of lanthanum. Whole genome resequencing for multiple lanthanide switch mutants identified several unique point mutations in a single gene encoding a TonB-dependent receptor, which we have named LanA. While the LanA TonB-dependent receptor is absolutely required for the lanthanide switch, it does not affect lanthanum uptake by the bacterium. Deletion of a separate lanthanide-repressible gene encoding a TonB protein had no effect on the lanthanide switch or on lanthanum uptake. The discovery of this novel component of the lanthanide regulatory system highlights the complexity of this circuit and suggests further components are likely involved.

2019-05-21 | GSE125909 | GEO

Gene expression changes in response to lanthanum concentration and lanthanide species in Beijerinckiaceae bacterium RH AL1

Project description:We show that lanthanum concentration and lanthanide species significantly affect gene expression under methylotrophic growth conditions. Using incubations with either lanthanum (La), neodymium (Nd), or a lanthanide cocktail, differential gene expression analysis revealed that up tp 41% of the encoded genes were differentially expressed.

2023-03-03 | E-MTAB-12015 | biostudies-arrayexpress

Treatment of a human lymphoblastoid cell line with the iron chelator deferoxamine

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2022-03-23 | GSE199077 | GEO

Discovery

Project description:Discovery

2022-01-11 | OEX00013698 | NODE

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| PRJNA449839 | ENA

RNA-Seq of MDA-MB-231 human triple-negative breast cancer cells treated with a copper chelator

Project description:We report the application of RNA-sequencing of MDA-MB-231 human triple-negative breast cancer cells treated with copper chelator Tetraethylenepentamine (TEPA) for 8 and 24 hours. We show transcriptome changes following copper chelation vs. control untreated cells.vs. control samples

2024-04-24 | GSE185760 | GEO

CITE-seq of LSK cells from aged mice after long-term iron chelator regimen

Project description:We found that iron chelation restored functional defects in aged HSC, including engraftment potential and platelet bias. To gain molecular insights into iron-dependent mechanism for sustaining HSC identity during aging, we performed Cellular Indexing of Transcriptomes and Epitopes by Sequencing (CITE-seq) with lineage (Lin)− Sca-1+ cKit+ (LSK) cells isolated from aged mice after long-term regimens with iron chelator Deferoxamine or vehicle control.

2024-05-02 | GSE232022 | GEO

Iron-sensitive RNA regulation by poly C binding proteins [chelator]

Project description:Iron-sensitive RNA regulation by poly C binding proteins [chelator]

| PRJNA1175600 | ENA