scholarly journals Enhancement of Nucleoside Production in Hirsutella sinensis Based on Biosynthetic Pathway Analysis

2017 ◽  
Vol 2017 ◽  
pp. 1-11 ◽  
Author(s):  
Zhi-Qiang Liu ◽  
Bo Zhang ◽  
Shan Lin ◽  
Peter James Baker ◽  
Mao-Sheng Chen ◽  
...  
Keyword(s):  
Pathway Analysis ◽  
Biosynthetic Pathway ◽  
Differential Expression Analysis ◽  
Guanosine Monophosphate ◽  
Biosynthetic Pathways ◽  
Dihydroorotate Dehydrogenase ◽  
Inosine Monophosphate Dehydrogenase ◽  
Nucleotide Biosynthesis ◽  
Pyrimidine Nucleosides ◽  
Inosine Triphosphate Pyrophosphatase

To enhance nucleoside production in Hirsutella sinensis, the biosynthetic pathways of purine and pyrimidine nucleosides were constructed and verified. The differential expression analysis showed that purine nucleoside phosphorylase, inosine monophosphate dehydrogenase, and guanosine monophosphate synthase genes involved in purine nucleotide biosynthesis were significantly upregulated 16.56-fold, 8-fold, and 5.43-fold, respectively. Moreover, dihydroorotate dehydrogenase, uridine nucleosidase, uridine/cytidine monophosphate kinase, and inosine triphosphate pyrophosphatase genes participating in pyrimidine nucleoside biosynthesis were upregulated 4.53-fold, 10.63-fold, 4.26-fold, and 5.98-fold, respectively. To enhance the nucleoside production, precursors for synthesis of nucleosides were added based on the analysis of biosynthetic pathways. Uridine and cytidine contents, respectively, reached 5.04 mg/g and 3.54 mg/g when adding 2 mg/mL of ribose, resulting in an increase of 28.6% and 296% compared with the control, respectively. Meanwhile, uridine and cytidine contents, respectively, reached 10.83 mg/g 2.12 mg/g when adding 0.3 mg/mL of uracil, leading to an increase of 176.3% and 137.1%, respectively. This report indicated that fermentation regulation was an effective way to enhance the nucleoside production in H. sinensis based on biosynthetic pathway analysis.

scholarly journals Evolution of alternative biosynthetic pathways for vitamin C following plastid acquisition in photosynthetic eukaryotes

eLife ◽  
2015 ◽  
Vol 4 ◽  
Author(s):  
Glen Wheeler ◽  
Takahiro Ishikawa ◽  
Varissa Pornsaksit ◽  
Nicholas Smirnoff
Keyword(s):  
Vitamin C ◽  
Biosynthetic Pathway ◽  
Critical Role ◽  
Biosynthetic Pathways ◽  
Oxygen Species ◽  
Photosynthetic Eukaryote ◽  
Alternative Pathways ◽  
Photosynthetic Eukaryotes ◽  
Gulonolactone Oxidase ◽  
Eukaryote Evolution

Ascorbic acid (vitamin C) is an enzyme co-factor in eukaryotes that also plays a critical role in protecting photosynthetic eukaryotes against damaging reactive oxygen species derived from the chloroplast. Many animal lineages, including primates, have become ascorbate auxotrophs due to the loss of the terminal enzyme in their biosynthetic pathway, l-gulonolactone oxidase (GULO). The alternative pathways found in land plants and Euglena use a different terminal enzyme, l-galactonolactone dehydrogenase (GLDH). The evolutionary processes leading to these differing pathways and their contribution to the cellular roles of ascorbate remain unclear. Here we present molecular and biochemical evidence demonstrating that GULO was functionally replaced with GLDH in photosynthetic eukaryote lineages following plastid acquisition. GULO has therefore been lost repeatedly throughout eukaryote evolution. The formation of the alternative biosynthetic pathways in photosynthetic eukaryotes uncoupled ascorbate synthesis from hydrogen peroxide production and likely contributed to the rise of ascorbate as a major photoprotective antioxidant.

scholarly journals Elevated Levels of DNA Strand Breaks Induced by a Base Analog in the Human Cell Line with the P32T ITPA Variant

2010 ◽  
Vol 2010 ◽  
pp. 1-11 ◽  
Author(s):  
Irina S.-R. Waisertreiger ◽  
Miriam R. Menezes ◽  
James Randazzo ◽  
Youri I. Pavlov
Keyword(s):  
Cell Line ◽  
Human Cell Line ◽  
Dna Breaks ◽  
Nucleotide Biosynthesis ◽  
Purine Base ◽  
Strand Breaks ◽  
Inosine Triphosphate Pyrophosphatase ◽  
Base Analog ◽  
Deoxynucleoside Triphosphate ◽  
Dna Strand

Base analogs are powerful antimetabolites and dangerous mutagens generated endogenously by oxidative stress, inflammation, and aberrant nucleotide biosynthesis. Human inosine triphosphate pyrophosphatase (ITPA) hydrolyzes triphosphates of noncanonical purine bases (i.e., ITP, dITP, XTP, dXTP, or their mimic: 6-hydroxyaminopurine (HAP) deoxynucleoside triphosphate) and thus regulates nucleotide pools and protects cells from DNA damage. We demonstrate that the model purine base analog HAP induces DNA breaks in human cells and leads to elevation of levels of ITPA. A human polymorphic allele of theITPA, 94C->A encodes for the enzyme with a P32T amino-acid change and leads to accumulation of nonhydrolyzed ITP. The polymorphism has been associated with adverse reaction to purine base-analog drugs. The level of both spontaneous and HAP-induced DNA breaks is elevated in the cell line with the ITPA P32T variant. The results suggested that human ITPA plays a pivotal role in the protection of DNA from noncanonical purine base analogs.

scholarly journals Biosynthesis of Caffeine Underlying the Diversity of Motif B’ Methyltransferase

2015 ◽  
Vol 10 (5) ◽  
pp. 1934578X1501000 ◽  
Author(s):  
Fumiyo Nakayama ◽  
Kouichi Mizuno ◽  
Misako Kato
Keyword(s):  
Substrate Specificity ◽  
Biosynthetic Pathway ◽  
Catalytic Properties ◽  
Biosynthetic Pathways ◽  
Methyl Transferase ◽  
Purine Alkaloids ◽  
Purine Alkaloid

Caffeine (1,3,7-trimethylxanthine) and theobromine (3,7-dimethylxanthine) are well-known purine alkaloids in Camellia, Coffea, Cola, Paullinia, Ilex, and Theobroma spp. The caffeine biosynthetic pathway depends on the substrate specificity of N-methyltransferases, which are members of the motif B’ methyl-transferase family. The caffeine biosynthetic pathways in purine alkaloid-containing plants might have evolved in parallel with one another, consistent with different catalytic properties of the enzymes involved in these pathways.

Enhancement of cordyceps polysaccharide production via biosynthetic pathway analysis in Hirsutella sinensis

2016 ◽  
Vol 92 ◽  
pp. 872-880 ◽  
Author(s):  
Shan Lin ◽  
Zhi-Qiang Liu ◽  
Peter James Baker ◽  
Ming Yi ◽  
Hui Wu ◽  
...  
Keyword(s):  
Pathway Analysis ◽  
Biosynthetic Pathway ◽  
Polysaccharide Production

scholarly journals Tiazofurin induction of mouse erythroleukemia cell hemoglobin production in the absence of commitment or changes in protooncogene expression

Blood ◽  
1989 ◽  
Vol 73 (2) ◽  
pp. 431-434 ◽  
Author(s):  
ML Sherman ◽  
TD Shafman ◽  
MS Colman ◽  
DW Kufe
Keyword(s):  
Cell Differentiation ◽  
Dependent Manner ◽  
Beta Globin ◽  
Inosine Monophosphate Dehydrogenase ◽  
Concentration Dependent Manner ◽  
Nucleotide Biosynthesis ◽  
Rna Transcripts ◽  
Erythroleukemia Cell ◽  
Hemoglobin Production ◽  
Mouse Erythroleukemia

Abstract Tiazofurin (2-beta-D-ribofuranosylthiazole-4-carboxamide, NSC 286193), is a synthetic nucleoside inhibitor of inosine monophosphate dehydrogenase and blocks guanine nucleotide biosynthesis. In the present study, we examined the effects of tiazofurin on mouse erythroleukemia (MEL) cell differentiation and protooncogene expression. Tiazofurin induced hemoglobin production in MEL cells in a concentration-dependent manner, as measured by an increase in benzidine staining. Northern blot analysis of MEL cells treated with 7 mumol/L tiazofurin demonstrated accumulation of both alpha- and beta-globin RNA transcripts. This induction of differentiation was blocked by the presence of exogenous guanosine (100 mumol/L). In contrast to the down- regulation of c-myc and c-myb RNA in MEL cells induced by dimethyl sulfoxide (DMSO) or hexamethylene bisacetamide (HMBA), there was no detectable change in levels of these transcripts after tiazofurin treatment. Furthermore, MEL cells induced by tiazofurin did not commit to terminal differentiation. These results suggest a role for guanine nucleotides, at least in part, in the regulation of MEL cell differentiation.

scholarly journals Bacterial terpene biosynthesis: challenges and opportunities for pathway engineering

2019 ◽  
Vol 15 ◽  
pp. 2889-2906 ◽  
Author(s):  
Eric J N Helfrich ◽  
Geng-Min Lin ◽  
Christopher A Voigt ◽  
Jon Clardy
Keyword(s):  
Biosynthetic Pathway ◽  
Pathway Engineering ◽  
Biosynthetic Pathways ◽  
Assembly Lines ◽  
Terpene Biosynthesis ◽  
Biotechnological Production ◽  
Genetic Potential ◽  
Challenges And Opportunities ◽  
Tailoring Enzymes ◽  
Single Enzyme

Terpenoids are the largest and structurally most diverse class of natural products. They possess potent and specific biological activity in multiple assays and against diseases, including cancer and malaria as notable examples. Although the number of characterized terpenoid molecules is huge, our knowledge of how they are biosynthesized is limited, particularly when compared to the well-studied thiotemplate assembly lines. Bacteria have only recently been recognized as having the genetic potential to biosynthesize a large number of complex terpenoids, but our current ability to associate genetic potential with molecular structure is severely restricted. The canonical terpene biosynthetic pathway uses a single enzyme to form a cyclized hydrocarbon backbone followed by modifications with a suite of tailoring enzymes that can generate dozens of different products from a single backbone. This functional promiscuity of terpene biosynthetic pathways renders terpene biosynthesis susceptible to rational pathway engineering using the latest developments in the field of synthetic biology. These engineered pathways will not only facilitate the rational creation of both known and novel terpenoids, their development will deepen our understanding of a significant branch of biosynthesis. The biosynthetic insights gained will likely empower a greater degree of engineering proficiency for non-natural terpene biosynthetic pathways and pave the way towards the biotechnological production of high value terpenoids.

scholarly journals Lactate Dehydrogenase B and Pyruvate Oxidation Pathway Associated With Carfilzomib-Related Cardiotoxicity in Multiple Myeloma Patients: Result of a Multi-Omics Integrative Analysis

2021 ◽  
Vol 8 ◽  
Author(s):  
Marwa Tantawy ◽  
Lakshmi Manasa Chekka ◽  
Yimei Huang ◽  
Timothy J. Garrett ◽  
Sonal Singh ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Lactate Dehydrogenase ◽  
Pathway Analysis ◽  
Differential Expression Analysis ◽  
The United States ◽  
Integrative Analysis ◽  
Cancer Center ◽  
Proteomic Profiling ◽  
Oxidation Pathway ◽  
Pyruvate Oxidation

Multiple myeloma (MM) is the second most frequent hematologic cancer in the United States. Carfilzomib (CFZ), an irreversible proteasome inhibitor being used to treat relapsed and refractory MM, has been associated with cardiotoxicity, including heart failure. We hypothesized that a multi-omics approach integrating data from different omics would provide insights into the mechanisms of CFZ-related cardiovascular adverse events (CVAEs). Plasma samples were collected from 13 MM patients treated with CFZ (including 7 with CVAEs and 6 with no CVAEs) at the University of Florida Health Cancer Center. These samples were evaluated in global metabolomic profiling, global proteomic profiling, and microRNA (miRNA) profiling. Integrative pathway analysis was performed to identify genes and pathways differentially expressed between patients with and without CVAEs. The proteomics analysis identified the up-regulation of lactate dehydrogenase B (LDHB) [fold change (FC) = 8.2, p = 0.01] in patients who experienced CVAEs. The metabolomics analysis identified lower plasma abundance of pyruvate (FC = 0.16, p = 0.0004) and higher abundance of lactate (FC = 2.4, p = 0.0001) in patients with CVAEs. Differential expression analysis of miRNAs profiling identified mir-146b to be up-regulatein (FC = 14, p = 0.046) in patients with CVAE. Pathway analysis suggested that the pyruvate fermentation to lactate pathway is associated with CFZ-CVAEs. In this pilot multi-omics integrative analysis, we observed the down-regulation of pyruvate and up-regulation of LDHB among patients who experienced CVAEs, suggesting the importance of the pyruvate oxidation pathway associated with mitochondrial dysfunction. Validation and further investigation in a larger independent cohort are warranted to better understand the mechanisms of CFZ-CVAEs.

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