Penicillium Arizonense as a Novel Producer Strain for Mycophenolic Acid and Expression Analysis of Biosynthesizing Gene Clusters

Abstract A novel potent mycophenolic acid (MPA) producer strain of the genus Penicillium was isolated from refrigerated Mozzarella cheese and identified as P. arizonenseHEWt1. The molecular mechanism of MPA production by this new isolate was our main target. To achieve this objective, we first isolated three MPA overproducer mutants by exposing the wild type to different doses of gamma-rays, and the fermentation conditions for the highest production of MPA by both the wild type and mutants were optimized. Then, orthologs of MPA gene clusters in P. brevicompactum were cloned and predicted from the genome of P. arizonense. Sequencing and bioinformatic analysis proved the presence of a cluster containing five putative genes in the P. arizonense HEWt1 genome ortholog to the MPA cluster, mpaA, mpaC, mpaF, mpaG, and mpaH. All predicted genes displayed 96-97% similarity with the related hypothetical protein of P. arizonense. The genes, mpaG, mpaC, and mpaF. represented 69%, 82%, 84%, respectively, similarity with their orthologous genes in P. brevicompactum, whereas mpaG and mpaA represented 75% and 79%, respectively, similarity to their orthologous genes in P. roqueforti. Gene expression analysis through quantitative rPCR indicated an increase in the transcription value of all annotated genes in the three mutants over the wild type. A highly significant increase in the gene expression of mpaC, mpaF, and mpaH was observed, with 8.4561±1.02, 5.6569±0.87, and 4.6268±0.18-fold increases, respectively, in P. arizonense-MT1 compared with wild-type. These results confirmed the potential participation of these genes in MPA biosynthesis and are the first report regarding the molecular mechanism of MPA production by P. arizonense.

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Metabolite and gene expression analysis reveal the molecular mechanism for petal colour variation in six Centaurea cyanus cultivars

Plant Physiology and Biochemistry ◽

10.1016/j.plaphy.2019.06.018 ◽

2019 ◽

Vol 142 ◽

pp. 22-33 ◽

Cited By ~ 2

Author(s):

Chengyan Deng ◽

Shanshan Li ◽

Chengyong Feng ◽

Yan Hong ◽

He Huang ◽

...

Keyword(s):

Gene Expression ◽

Molecular Mechanism ◽

Expression Analysis ◽

Gene Expression Analysis ◽

Colour Variation ◽

Petal Colour ◽

Centaurea Cyanus

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In silico gene expression analysis reveals glycolysis and acetate anaplerosis in IDH1 wild-type glioma and lactate and glutamate anaplerosis in IDH1-mutated glioma

Oncotarget ◽

10.18632/oncotarget.17106 ◽

2017 ◽

Vol 8 (30) ◽

pp. 49165-49177 ◽

Cited By ~ 31

Author(s):

Mohammed Khurshed ◽

Remco J. Molenaar ◽

Krissie Lenting ◽

William P. Leenders ◽

Cornelis J.F. van Noorden

Keyword(s):

Gene Expression ◽

Expression Analysis ◽

In Silico ◽

Gene Expression Analysis ◽

Wild Type

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NF-E2 domination over Nrf2 promotes ROS accumulation and megakaryocytic maturation

Blood ◽

10.1182/blood-2009-05-223107 ◽

2010 ◽

Vol 115 (3) ◽

pp. 677-686 ◽

Cited By ~ 63

Author(s):

Hozumi Motohashi ◽

Momoko Kimura ◽

Rie Fujita ◽

Ai Inoue ◽

Xiaoqing Pan ◽

...

Keyword(s):

Gene Expression ◽

Target Genes ◽

Functional Relationship ◽

Gene Clusters ◽

Oxidative Stress Response ◽

Oxygen Species ◽

Wild Type ◽

Ros Accumulation ◽

Stress Responsive Genes ◽

And Oxidative Stress

Abstract In megakaryocytes, the maturation process and oxidative stress response appear to be closely related. It has been suggested that increased oxygen tension and reactive oxygen species (ROS) promote megakaryopoiesis and that the expression of stress-responsive genes responsible for ROS elimination declines during megakaryocytic maturation. NF-E2 p45 is an essential regulator of megakaryopoiesis, whereas Nrf2 is a key activator of stress-responsive genes. Because p45 and Nrf2 have similar DNA-binding specificities, we hypothesized that p45 competes with Nrf2 to repress stress-responsive genes and achieves favorable intracellular conditions to allow ROS to be efficiently used as signaling molecules. We conducted comprehensive gene expression profiling with wild-type and p45-null megakaryocytes and examined the functional relationship between p45 and Nrf2. We found that 2 characteristic gene clusters are defined within p45 target genes: platelet genes and cytoprotective genes. The former are unique targets activated by p45, whereas the latter are common targets of p45 and Nrf2. Further analysis suggested that, as a less efficacious activator, p45 maintains moderate expression of cytoprotective genes through competing with Nrf2 and promotes ROS accumulation. Increased ROS enhanced platelet gene expression. These results suggest that p45 dominates over Nrf2 to enhance megakaryocytic maturation by promoting ROS accumulation.

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Engineering of red cells of Arabidopsis thaliana and comparative genome-wide gene expression analysis of red cells versus wild-type cells

Planta ◽

10.1007/s00425-010-1335-2 ◽

2011 ◽

Vol 233 (4) ◽

pp. 787-805 ◽

Cited By ~ 22

Author(s):

Ming-Zhu Shi ◽

De-Yu Xie

Keyword(s):

Gene Expression ◽

Arabidopsis Thaliana ◽

Expression Analysis ◽

Gene Expression Analysis ◽

Red Cells ◽

Wild Type ◽

Comparative Genome ◽

Genome Wide ◽

Genome Wide Gene Expression

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Metabolic Profiling and Gene Expression Analysis Unveil Differences in Flavonoid and Lipid Metabolisms Between ‘Huapi’ Kumquat (Fortunella crassifolia Swingle) and Its Wild Type

Frontiers in Plant Science ◽

10.3389/fpls.2021.759968 ◽

2021 ◽

Vol 12 ◽

Author(s):

Qiaoli Ma ◽

Yongwei Hu ◽

Xinghua Dong ◽

Gaofeng Zhou ◽

Xiao Liu ◽

...

Keyword(s):

Gene Expression ◽

Expression Analysis ◽

Metabolic Profiling ◽

Gene Expression Analysis ◽

Structural Genes ◽

Wild Type ◽

Gene Expressions ◽

Oil Glands ◽

Light Color ◽

Metabolomics Analysis

To elucidate the mechanism underlying special characteristic differences between a spontaneous seedling mutant ‘Huapi’ kumquat (HP) and its wild-type ‘Rongan’ kumquat (RA), the fruit quality, metabolic profiles, and gene expressions of the peel and flesh were comprehensively analyzed. Compared with RA, HP fruit has distinctive phenotypes such as glossy peel, light color, and few amounts of oil glands. Interestingly, HP also accumulated higher flavonoid (approximately 4.1-fold changes) than RA. Based on metabolomics analysis, we identified 201 differential compounds, including 65 flavonoids and 37 lipids. Most of the differential flavonoids were glycosylated by hexoside and accumulated higher contents in the peel but lower in the flesh of HP than those of RA fruit. For differential lipids, most of them belonged to lysophosphatidycholines (LysoPCs) and lysophosphatidylethanolamines (LysoPEs) and exhibited low abundance in both peel and flesh of HP fruit. In addition, structural genes associated with the flavonoid and lipid pathways were differentially regulated between the two kumquat varieties. Gene expression analysis also revealed the significant roles of UDP-glycosyltransferase (UGT) and phospholipase genes in flavonoid and glycerophospholipid metabolisms, respectively. These findings provide valuable information for interpreting the mutation mechanism of HP kumquat.

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Mechanisms of Targeting the MDM2-p53-FOXM1 Axis in Well-Differentiated Intestinal Neuroendocrine Tumors

Neuroendocrinology ◽

10.1159/000481506 ◽

2017 ◽

Vol 107 (1) ◽

pp. 1-23

Author(s):

Franziska Briest ◽

Irina Grass ◽

Dagmar Sedding ◽

Markus Möbs ◽

Friederike Christen ◽

...

Keyword(s):

Gene Expression ◽

Western Blot ◽

Neuroendocrine Tumors ◽

Expression Analysis ◽

Gene Expression Analysis ◽

Neuroendocrine Neoplasms ◽

Wild Type ◽

Frequent Event ◽

P53 Response

Background/Aims: The tumor suppressor p53 is rarely mutated in gastroenteropancreatic neuroendocrine neoplasms (GEP-NEN) but they frequently show a strong expression of negative regulators of p53, rendering these tumors excellent targets for a p53 recovery therapy. Therefore, we analyzed the mechanisms of a p53 recovery therapy on intestinal neuroendocrine tumors in vitro and in vivo.Methods: By Western blot and immunohistochemistry, we found that in GEP-NEN biopsy material overexpression of MDM2 was present in intestinal NEN. Therefore, we analyzed the effect of a small-molecule inhibitor, nutlin-3a, in p53 wild-type and mutant GEP-NEN cell lines by proliferation assay, flow cytometry, immunofluorescence, Western blot, and by multiplex gene expression analysis. Finally, we analyzed the antitumor effect of nutlin-3a in a xenograft mouse model in vivo. During the study, the tumor volume was determined. Results: The midgut wild-type cell line KRJ-I responded to the treatment with cell cycle arrest and apoptosis. By gene expression analysis, we could demonstrate that nutlins reactivated an antiproliferative p53 response. KRJ-I-derived xenograft tumors showed a significantly decreased tumor growth upon treatment with nutlin-3a in vivo. Furthermore, our data suggest that MDM2 also influences the expression of the oncogene FOXM1 in a p53-independent manner. Subsequently, a combined treatment of nutlin-3a and cisplatin (as chemoresistance model) resulted in synergistically enhanced antiproliferative effects. Conclusion: In summary, MDM2 overexpression is a frequent event in p53 wild-type intestinal neuroendocrine neoplasms and therefore recovery of a p53 response might be a novel personalized treatment approach in these tumors.

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