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Discovery, characterization, and metabolic engineering of Rieske non-heme iron monooxygenases for guaiacol O-demethylation

ABSTRACT: Discovery, characterization, and metabolic engineering of Rieske non-heme iron monooxygenases for guaiacol O-demethylation

INSTRUMENT(S): Q Exactive Plus

ORGANISM(S): Novosphingobium Aromaticivorans (ncbitaxon:48935)

SUBMITTER: Joshua K. Michener Gregg T. Beckham

PROVIDER: MSV000088263 | MassIVE | Mon Oct 25 15:24:00 BST 2021

SECONDARY ACCESSION(S): PXD029346

REPOSITORIES: MassIVE

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Iron-Heme-Bach1 Axis Is Involved In Erythroblast Adaptation To Iron Deficiency

Project description:Iron plays the central role in the oxygen transport by the erythrocyte as a constituent of heme and hemoglobin. The importance of iron and heme also resides in their regulatory roles during erythroblast maturation. The transcription factor Bach1 may be involved in their regulatory roles since it is inactivated by direct binding of heme. To address whether Bach1 is involved in the responses of erythroblasts to iron status, low iron conditions that induced severe iron deficiency in mice were established. Under iron deficiency, extensive gene expression changes and mitophagy disorder were induced during maturation of erythroblasts. Bach1 mice showed more severe iron deficiency anemia in the developmental phase of mice and a retarded recovery once iron was replenished when compared with wild-type mice. In the absence of Bach1, the expression of globin genes and Hmox1 (encoding heme oxygenase-1) was de-repressed in erythroblasts under iron deficiency, suggesting that Bach1 represses these genes in erythroblasts under iron deficiency to balance the levels of heme and globin. Moreover, an increase in genome-wide DNA methylation was observed in erythroblasts of Bach1–/– mice under iron deficiency. These findings reveal the principle role of iron as a regulator of gene expression in erythroblast maturation and suggest that the iron-heme-Bach1 axis is important for a proper adaptation of erythroblast to iron deficiency to avoid toxic aggregates of non-heme globin.

2016-12-14 | GSE78955 | GEO

Transcriptomic analysis of an iron-resistant Saccharomyces cerevisiae mutant obtained by evolutionary engineering

Project description:Iron-resistant Saccharomyces cerevisiae mutant was obtained by evolutionary engineering selection strategy. The mutant obtained “M8FE” is much more resistant to iron stress than the reference strain which was used to select this mutant. Mutant can resist up to 35mM Iron* stress whereas the reference strain cannot. Whole-genome microarray analysis might be promising to identify the iron resistance mechanisms and stress response upon high levels of iron in the yeast cells. Iron-resistant mutant is also cross resistant to Cobalt, Chromium and Nickel but sensitive to Zinc. * refers to [NH4]2[Fe][SO4]2 and FeCl2.

2014-09-11 | GSE61317 | GEO

Transcriptomic analysis of an iron-resistant Saccharomyces cerevisiae mutant obtained by evolutionary engineering

Project description:Iron-resistant Saccharomyces cerevisiae mutant was obtained by evolutionary engineering selection strategy. The mutant obtained M-bM-^@M-^\M8FEM-bM-^@M-^] is much more resistant to iron stress than the reference strain which was used to select this mutant. Mutant can resist up to 35mM Iron* stress whereas the reference strain cannot. Whole-genome microarray analysis might be promising to identify the iron resistance mechanisms and stress response upon high levels of iron in the yeast cells. Iron-resistant mutant is also cross resistant to Cobalt, Chromium and Nickel but sensitive to Zinc. * refers to [NH4]2[Fe][SO4]2 and FeCl2. The reference Saccharomyces cerevisiae strain and the iron-resistant mutant were grown in minimal medium to an Optical Density (OD600) of 1.00 which correspond to the logarithmic growth phase of the yeast cells. Cultures were harvested and whole RNA isolation was carried out. The experiment was repeated three times.

2014-09-11 | E-GEOD-61317 | biostudies-arrayexpress

Transcriptional Profile of Haemophilus influenzae: Effects of Iron and Heme

Project description:Haemophilus influenzae frequently causes human disease, and humans are it’s sole niche. This bacterium has an absolute requirement for both a porphyrin and an iron source for aerobic growth, and exogenous heme can satisfy both requirements. Heme and iron can be acquired by H. influenzae from free or human protein-bound sources. The ability to selectively regulate the acquisition of heme and iron from physiological sources is a major virulence determinant for this microorganism. We utilized whole genome arrays to identify the full set of H. influenzae Rd KW20 iron and heme regulated genes. Condition specific RNA was derived from cells starved for both heme and iron and cells from the same culture 20 mins after the addition of exogenous iron and heme. The results identified 162 genes with a change in transcription ≥ 1.5 fold. Eighty genes in 42 operons were preferentially expressed under iron/ heme starvation; 82 genes in 50 operons were preferentially expressed under iron/heme replete conditions. In each case, all genes contained within the operon were co-regulated. The former group included genes encoding proteins known to have a role in iron and heme uptake as well as several hypothetical ORFs. Enzymes involved in the gluconeogenesis pathway and glycogen biosynthesis were also upregulated. The genes showing increased transcription immediately after the addition of iron and heme primarily encode proteins involved with aerobic respiration and protein biosynthesis, consistent with a relaxation of starvation. Genomic transcriptional profiling provides a more complete understanding of the effects of iron and heme availability. Keywords: Transcription analyses

2006-07-28 | GSE5061 | GEO

Obesity, Iron Regulation and Colorectal Cancer Risk

Project description:Obesity is an independent risk factor for colorectal cancer (CRC) although the underlying mechanisms have not been elucidated. Dietary nutrients play a key role in both the prevention and promotion of CRC. While iron is an essential nutrient, excess iron is associated with carcinogenesis. Unlike the systemic compartment, the intestinal lumen lacks an efficient system to regulate iron. In conditions when dietary iron malabsorption and intestinal inflammation co-exist, greater luminal iron is associated with increased intestinal inflammation and a shift in the gut microbiota to more pro-inflammatory strains. However, treatments designed to reduce luminal, including diet restriction and chelation, are associated with lower intestinal inflammation and the colonization of protective gut microbes. Obesity is associated with inflammation-induced, hepcidin-mediated, iron metabolism dysfunction characterized by iron deficiency and dietary iron malabsorption. Obesity is also linked to intestinal inflammation. Currently, there is a fundamental gap in understanding how altered iron metabolism impacts CRC risk in obesity. The investigator’s objective is to conduct a crossover controlled feeding trial of: 1) a "Typical American" diet with "high" heme/non-heme iron", 2) a "Typical American" diet with "low" iron, and 3) a Mediterranean diet with "high" non heme iron and examine effects on colonic and systemic inflammation and the gut microbiome.

| 2274754 | ecrin-mdr-crc

Heme Deficient vs Wild Type in Low Iron

Project description:Heme Deficient or Wild Type (normal heme) for 6 hrs with iron chelation by BPS. Keywords: Cell Type Comparison

2005-10-18 | GSE3470 | GEO

Gene expression profile at single cell level of iron positive and iron negative cells from subcutaneous implanted syngeneic fibrosarcoma tumors in C57BL/6 mice.

Project description:Iron-rich tumor-associated macrophages (iTAMs) are characterized by high intracellular iron, heme metabolism, and expression of the endothelin receptor B. iTAMs promote angiogenesis and immunosuppression in tumors. Heme-mediated degradation of the transcriptional repressor BACH1 induces the iTAM transcriptional program in macrophages.

2024-08-30 | GSE269203 | GEO

Iron and Heme Coordinate Erythropoiesis through HRI-Mediated Regulation of Protein Translation and Gene Expression

Project description:Iron and heme play central roles in red blood cell production. However, the mechanisms by which iron and heme levels coordinate erythropoiesis remain incompletely understood. HRI is a heme-regulated kinase that controls translation by phosphorylating eIF2a. Here, we investigate the global impact of iron, heme and HRI on protein translation in vivo in murine primary erythroblasts using ribosome profiling. By defining the underlying changes in translation during iron and HRI deficiencies, we validate known regulators of this process, including Atf4, and identify novel pathways such as co-regulation of ribosomal protein mRNA translation. Surprisingly, we found that heme and HRI pathways, but not iron-regulated pathways, mediate the major protein translational and transcriptional responses to iron deficiency in erythroblasts in vivo and thereby identify previously unappreciated regulators of erythropoiesis. Our genome-wide study uncovers the major impact of the HRI-mediated integrated stress response for the adaptation to iron deficiency anemia.

2018-09-03 | GSE119365 | GEO

Investigation of Bach1 function by heme-iron homeostasis in bone marrow derived macrophage

Project description:Macrophages are central in regulating iron homeostasis. Transcription repressor Bach1 regulates by heme. Here we investigated the relationship between heme-regulated Bach1 and bone marrow derived macrophage. We found that Bach1 KO macrophage showed that up-regulated genes were the process that iron-heme homeostasis and maintenance related gene compared with WT. Our results suggest that Bach1 expression is important to the heme homeostasis and maintenance in the bone marrow derived macrophage.

2019-03-30 | GSE79717 | GEO

Heme Deficient vs Wild Type in Low Iron

Project description:Heme Deficient or Wild Type (normal heme) for 6 hrs with iron chelation by BPS. Single Experiment with Probe Reversal 1. GSM78518 (Cy3) vs GSM78519 (Cy5) 2. GSM78520 (Cy3) vs GSM78521 (Cy5)

2010-06-30 | E-GEOD-3470 | biostudies-arrayexpress

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