scholarly journals Phenolic Amides Are Potent Inhibitors ofDe NovoNucleotide Biosynthesis

2015 ◽  
Vol 81 (17) ◽  
pp. 5761-5772 ◽  
Author(s):  
Tippapha Pisithkul ◽  
Tyler B. Jacobson ◽  
Thomas J. O'Brien ◽  
David M. Stevenson ◽  
Daniel Amador-Noguez
Keyword(s):  
Phenolic Compounds ◽  
De Novo ◽  
Plant Biomass ◽  
Value Added ◽  
Metabolic Effects ◽  
Efficient Production ◽  
Biosynthetic Pathways ◽  
Nucleotide Biosynthesis ◽  
Phenolic Amides ◽  
The Impact

ABSTRACTAn outstanding challenge toward efficient production of biofuels and value-added chemicals from plant biomass is the impact that lignocellulose-derived inhibitors have on microbial fermentations. Elucidating the mechanisms that underlie their toxicity is critical for developing strategies to overcome them. Here, usingEscherichia colias a model system, we investigated the metabolic effects and toxicity mechanisms of feruloyl amide and coumaroyl amide, the predominant phenolic compounds in ammonia-pretreated biomass hydrolysates. Using metabolomics, isotope tracers, and biochemical assays, we showed that these two phenolic amides act as potent and fast-acting inhibitors of purine and pyrimidine biosynthetic pathways. Feruloyl or coumaroyl amide exposure leads to (i) a rapid buildup of 5-phosphoribosyl-1-pyrophosphate (PRPP), a key precursor in nucleotide biosynthesis, (ii) a rapid decrease in the levels of pyrimidine biosynthetic intermediates, and (iii) a long-term generalized decrease in nucleotide and deoxynucleotide levels. Tracer experiments using13C-labeled sugars and [15N]ammonia demonstrated that carbon and nitrogen fluxes into nucleotides and deoxynucleotides are inhibited by these phenolic amides. We found that these effects are mediated via direct inhibition of glutamine amidotransferases that participate in nucleotide biosynthetic pathways. In particular, feruloyl amide is a competitive inhibitor of glutamine PRPP amidotransferase (PurF), which catalyzes the first committed step inde novopurine biosynthesis. Finally, external nucleoside supplementation prevents phenolic amide-mediated growth inhibition by allowing nucleotide biosynthesis via salvage pathways. The results presented here will help in the development of strategies to overcome toxicity of phenolic compounds and facilitate engineering of more efficient microbial producers of biofuels and chemicals.

scholarly journals Cell-based and cell-free biocatalysis for the production of d-glucaric acid

2020 ◽  
Vol 13 (1) ◽  
Author(s):  
Lu-Zhou Chen ◽  
Si-Ling Huang ◽  
Jin Hou ◽  
Xue-Ping Guo ◽  
Feng-Shan Wang ◽  
...  
Keyword(s):  
Metabolic Pathways ◽  
De Novo ◽  
Value Added ◽  
Host Cells ◽  
Efficient Production ◽  
Glucaric Acid ◽  
A Value ◽  
Potential Applications ◽  
Increasing Demand

Abstractd-Glucaric acid (GA) is a value-added chemical produced from biomass, and has potential applications as a versatile platform chemical, food additive, metal sequestering agent, and therapeutic agent. Marketed GA is currently produced chemically, but increasing demand is driving the search for eco-friendlier and more efficient production approaches. Cell-based production of GA represents an alternative strategy for GA production. A series of synthetic pathways for GA have been ported into Escherichia coli, Saccharomyces cerevisiae and Pichia pastoris, respectively, and these engineered cells show the ability to synthesize GA de novo. Optimization of the GA metabolic pathways in host cells has leapt forward, and the titer and yield have increased rapidly. Meanwhile, cell-free multi-enzyme catalysis, in which the desired pathway is constructed in vitro from enzymes and cofactors involved in GA biosynthesis, has also realized efficient GA bioconversion. This review presents an overview of studies of the development of cell-based GA production, followed by a brief discussion of potential applications of biosensors that respond to GA in these biosynthesis routes.

scholarly journals De novo biosynthesis of bioactive isoflavonoids by engineered yeast cell factories

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Quanli Liu ◽  
Yi Liu ◽  
Gang Li ◽  
Otto Savolainen ◽  
Yun Chen ◽  
...  
Keyword(s):  
Natural Products ◽  
Yeast Cell ◽  
De Novo ◽  
Structural Complexity ◽  
Value Added ◽  
Fine Tuning ◽  
Attractive Alternative ◽  
Efficient Production ◽  
De Novo Biosynthesis ◽  
Cell Factories

AbstractIsoflavonoids comprise a class of plant natural products with great nutraceutical, pharmaceutical and agricultural significance. Their low abundance in nature and structural complexity however hampers access to these phytochemicals through traditional crop-based manufacturing or chemical synthesis. Microbial bioproduction therefore represents an attractive alternative. Here, we engineer the metabolism of Saccharomyces cerevisiae to become a platform for efficient production of daidzein, a core chemical scaffold for isoflavonoid biosynthesis, and demonstrate its application towards producing bioactive glucosides from glucose, following the screening-reconstruction-application engineering framework. First, we rebuild daidzein biosynthesis in yeast and its production is then improved by 94-fold through screening biosynthetic enzymes, identifying rate-limiting steps, implementing dynamic control, engineering substrate trafficking and fine-tuning competing metabolic processes. The optimized strain produces up to 85.4 mg L−1 of daidzein and introducing plant glycosyltransferases in this strain results in production of bioactive puerarin (72.8 mg L−1) and daidzin (73.2 mg L−1). Our work provides a promising step towards developing synthetic yeast cell factories for de novo biosynthesis of value-added isoflavonoids and the multi-phased framework may be extended to engineer pathways of complex natural products in other microbial hosts.

AML1/RUNX1 mutations in 470 adult patients with de novo acute myeloid leukemia: prognostic implication and interaction with other gene alterations

Blood ◽  
2009 ◽  
Vol 114 (26) ◽  
pp. 5352-5361 ◽  
Author(s):  
Jih-Luh Tang ◽  
Hsin-An Hou ◽  
Chien-Yuan Chen ◽  
Chieh-Yu Liu ◽  
Wen-Chien Chou ◽  
...  
Keyword(s):  
Overall Survival ◽  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
De Novo ◽  
Remission Rate ◽  
Adult Patients ◽  
Poor Prognostic Factor ◽  
The Impact ◽  
Runx1 Mutation ◽  
Acute Myeloid

AbstractSomatic mutation of the AML1/RUNX1(RUNX1) gene is seen in acute myeloid leukemia (AML) M0 subtype and in AML transformed from myelodysplastic syndrome, but the impact of this gene mutation on survival in AML patients remains unclear. In this study, we sought to determine the clinical implications of RUNX1 mutations in 470 adult patients with de novo non-M3 AML. Sixty-three distinct RUNX1 mutations were identified in 62 persons (13.2%); 32 were in N-terminal and 31, C-terminal. The RUNX1 mutation was closely associated with male sex, older age, lower lactic dehydrogenase value, French-American-British M0/M1 subtypes, and expression of HLA-DR and CD34, but inversely correlated with CD33, CD15, CD19, and CD56 expression. Furthermore, the mutation was positively associated with MLL/PTD but negatively associated with CEBPA and NPM1 mutations. AML patients with RUNX1 mutations had a significantly lower complete remission rate and shorter disease-free and overall survival than those without the mutation. Multivariate analysis demonstrated that RUNX1 mutation was an independent poor prognostic factor for overall survival. Sequential analysis in 133 patients revealed that none acquired novel RUNX1 mutations during clinical courses. Our findings provide evidence that RUNX1 mutations are associated with distinct biologic and clinical characteristics and poor prognosis in patients with de novo AML.

scholarly journals Dissecting cellobiose metabolic pathway and its application in biorefinery through consolidated bioprocessing in Myceliophthora thermophila

2019 ◽  
Vol 6 (1) ◽  
Author(s):  
Jingen Li ◽  
Shuying Gu ◽  
Zhen Zhao ◽  
Bingchen Chen ◽  
Qian Liu ◽  
...  
Keyword(s):  
Malic Acid ◽  
Plant Biomass ◽  
Consolidated Bioprocessing ◽  
Cellulase Activity ◽  
Industrial Applications ◽  
Efficient Production ◽  
Myceliophthora Thermophila ◽  
Final Strain ◽  
Cellobiose Metabolism ◽  
Cost Efficient

Abstract Background Lignocellulosic biomass has long been recognized as a potential sustainable source for industrial applications. The costs associated with conversion of plant biomass to fermentable sugar represent a significant barrier to the production of cost-competitive biochemicals. Consolidated bioprocessing (CBP) is considered a potential breakthrough for achieving cost-efficient production of biomass-based fuels and commodity chemicals. During the degradation of cellulose, cellobiose (major end-product of cellulase activity) is catabolized by hydrolytic and phosphorolytic pathways in cellulolytic organisms. However, the details of the two intracellular cellobiose metabolism pathways in cellulolytic fungi remain to be uncovered. Results Using the engineered malic acid production fungal strain JG207, we demonstrated that the hydrolytic pathway by β-glucosidase and the phosphorolytic pathway by phosphorylase are both used for intracellular cellobiose metabolism in Myceliophthora thermophila, and the yield of malic acid can benefit from the energy advantages of phosphorolytic cleavage. There were obvious differences in regulation of the two cellobiose catabolic pathways depending on whether M. thermophila JG207 was grown on cellobiose or Avicel. Disruption of Mtcpp in strain JG207 led to decreased production of malic acid under cellobiose conditions, while expression levels of all three intracellular β-glucosidase genes were significantly up-regulated to rescue the impairment of the phosphorolytic pathway under Avicel conditions. When the flux of the hydrolytic pathway was reduced, we found that β-glucosidase encoded by bgl1 was the dominant enzyme in the hydrolytic pathway and deletion of bgl1 resulted in significant enhancement of protein secretion but reduction of malate production. Combining comprehensive manipulation of both cellobiose utilization pathways and enhancement of cellobiose uptake by overexpression of a cellobiose transporter, the final strain JG412Δbgl2Δbgl3 produced up to 101.2 g/L and 77.4 g/L malic acid from cellobiose and Avicel, respectively, which corresponded to respective yields of 1.35 g/g and 1.03 g/g, representing significant improvement over the starting strain JG207. Conclusions This is the first report of detailed investigation of intracellular cellobiose catabolism in cellulolytic fungus M. thermophila. These results provide insights that can be applied to industrial fungi for production of biofuels and biochemicals from cellobiose and cellulose.

Open Door System and Endogenous Growth in Indian Economy: An Empirical Analysis on the Role of Human Capital and R&D in Explaining Industrial Productivity

2021 ◽  
Vol 46 (1) ◽  
pp. 24-37
Author(s):  
Arjun K. ◽  
Sanjay Kumar ◽  
A. Sankaran ◽  
Mousumi Das
Keyword(s):  
Human Capital ◽  
Exchange Rate ◽  
Real Exchange Rate ◽  
Endogenous Growth ◽  
Value Added ◽  
Capital Formation ◽  
Knowledge Capital ◽  
Test Technique ◽  
Long Run ◽  
The Impact

The present study investigates the impact of human capital, knowledge capital which is a function of human capital, and real exchange rate scenario in explaining long-run industrial total factor productivity (TFP) from 1980 to 2015 on the theoretical basis of the open endogenous growth model. The variables employed in the contemporary study include manufacturing value added (MNVA) as industrial output measure, gross fixed capital formation (GFCF) as a measure of capital and labour input which is measured using employment data. Gross enrolment ratio (GER) is taken as a measure for human capital formation, expenditure on research and development (R&D) as a proxy for knowledge capital, and real exchange rate indicates global economic shocks. The study involves estimating TFP for Industrial Sector during the post-liberalization period by employing Cobb-Douglas production function. The ARDL bounds test technique for cointegration revealed long-run relation among the varying factors studied. The Toda-Yamamoto causality test concluded bi-directional causality running between, R&D expenditure and Industrial TFP which sends a strong signal to the policymakers for a well-framed long-term integrated approach for human & knowledge capital formation which will act as a strong impetus for manufacturing firms to come up in terms of augmenting production and productivity and expanding foreign market horizon. JEL Classification: D24, E2, J24

scholarly journals Effect of Ni(NO3)2 Pretreatment on the Pyrolysis of Organsolv Lignin Derived from Corncob Residue

Processes ◽  
2020 ◽  
Vol 9 (1) ◽  
pp. 23
Author(s):  
Wenli Wang ◽  
Yichen Liu ◽  
Yue Wang ◽  
Longfei Liu ◽  
Changwei Hu
Keyword(s):  
Sustainable Development ◽  
Fixed Bed ◽  
Value Added ◽  
Bio Oil ◽  
Fuels And Chemicals ◽  
Gas Products ◽  
Work Samples ◽  
Nickel Species ◽  
The Impact ◽  
Selective Formation

The thermal degradation of lignin for value-added fuels and chemicals is important for environment improvement and sustainable development. The impact of pretreatment and catalysis of Ni(NO3)2 on the pyrolysis behavior of organsolv lignin were studied in the present work. Samples were pyrolyzed at 500 ∘C with an upward fixed bed, and the characteristics of bio-oil were determined. After pretreatment by Ni(NO3)2, the yield of monophenols increased from 23.3 wt.% to 30.2 wt.% in “Ni-washed” and decreased slightly from 23.3 wt.% to 20.3 wt.% in “Ni-unwashed”. Meanwhile, the selective formation of vinyl-monophenols was promoted in “Ni-unwashed”, which indicated that the existence of nickel species promoted the dehydration of C-OH and breakage of C-C in pyrolysis. In comparison with “Water”, HHV of bio-oil derived from “Ni-unwashed” slightly increased from 27.94 mJ/kg to 28.46 mJ/kg, suggesting that the lowering of oxygen content in bio-oil is associated with improved quality. Furthermore, the content of H2 in gas products dramatically increased from 2.0% to 7.6% and 17.1%, respectively.

scholarly journals The influence of advance speed on overburden movement characteristics in longwall coal mining: insight from theoretical analysis and physical simulation

2021 ◽  
Vol 18 (1) ◽  
pp. 163-176
Author(s):  
Penghua Han ◽  
Cun Zhang ◽  
Zhaopeng Ren ◽  
Xiang He ◽  
Sheng Jia
Keyword(s):  
Physical Simulation ◽  
Impact Load ◽  
Main Roof ◽  
Longwall Face ◽  
Mine Safety ◽  
Efficient Production ◽  
Time Space ◽  
Mining Pressure ◽  
The Impact ◽  
Advance Speed

Abstract The advance speed of a longwall face is an essential factor affecting the mining pressure and overburden movement, and an effective approach for choosing a reasonable advance speed to realise coal mine safety and efficient production is needed. To clarify the influence of advance speed on the overburden movement law of a fully mechanised longwall face, a time-space subsidence model of overburden movement is established by the continuous medium analysis method. The movement law of overburden in terms of the advance speed is obtained, and mining stress characteristics at different advance speeds are reasonably explained. The theoretical results of this model are further verified by a physical simulation experiment. The results support the following conclusions. (i) With increasing advance speed of the longwall face, the first (periodic) rupture interval of the main roof and the key stratum increase, while the subsidence of the roof, the fracture angle and the rotation angle of the roof decrease. (ii) With increasing advance speed, the roof displacement range decreases gradually, and the influence range of the advance speed on the roof subsidence is 75 m behind the longwall face. (iii) An increase in the advance speed of the longwall face from 4.89 to 15.23 m/d (daily advancing of the longwall face) results in a 3.28% increase in the impact load caused by the sliding instability of the fractured rock of the main roof and a 5.79% decrease in the additional load caused by the rotation of the main roof, ultimately resulting in a 9.63% increase in the average dynamic load coefficient of the support. The roof subsidence model based on advance speed is proposed to provide theoretical support for rational mining design and mining-pressure-control early warning for a fully mechanised longwall face.

scholarly journals Epigenetic Changes in Host Ribosomal DNA Promoter Induced by an Asymptomatic Plant Virus Infection

Biology ◽  
2020 ◽  
Vol 9 (5) ◽  
pp. 91 ◽  
Author(s):  
Miryam Pérez-Cañamás ◽  
Elizabeth Hevia ◽  
Carmen Hernández
Keyword(s):  
Gene Silencing ◽  
Ribosomal Dna ◽  
Plant Virus ◽  
Dna Methyltransferase ◽  
Cytosine Methylation ◽  
De Novo ◽  
Methylation Pattern ◽  
Transcriptional Gene Silencing ◽  
Post Transcriptional Gene Silencing ◽  
The Impact

DNA cytosine methylation is one of the main epigenetic mechanisms in higher eukaryotes and is considered to play a key role in transcriptional gene silencing. In plants, cytosine methylation can occur in all sequence contexts (CG, CHG, and CHH), and its levels are controlled by multiple pathways, including de novo methylation, maintenance methylation, and demethylation. Modulation of DNA methylation represents a potentially robust mechanism to adjust gene expression following exposure to different stresses. However, the potential involvement of epigenetics in plant-virus interactions has been scarcely explored, especially with regard to RNA viruses. Here, we studied the impact of a symptomless viral infection on the epigenetic status of the host genome. We focused our attention on the interaction between Nicotiana benthamiana and Pelargonium line pattern virus (PLPV, family Tombusviridae), and analyzed cytosine methylation in the repetitive genomic element corresponding to ribosomal DNA (rDNA). Through a combination of bisulfite sequencing and RT-qPCR, we obtained data showing that PLPV infection gives rise to a reduction in methylation at CG sites of the rDNA promoter. Such a reduction correlated with an increase and decrease, respectively, in the expression levels of some key demethylases and of MET1, the DNA methyltransferase responsible for the maintenance of CG methylation. Hypomethylation of rDNA promoter was associated with a five-fold augmentation of rRNA precursor levels. The PLPV protein p37, reported as a suppressor of post-transcriptional gene silencing, did not lead to the same effects when expressed alone and, thus, it is unlikely to act as suppressor of transcriptional gene silencing. Collectively, the results suggest that PLPV infection as a whole is able to modulate host transcriptional activity through changes in the cytosine methylation pattern arising from misregulation of methyltransferases/demethylases balance.

Impact of lipoprotein(a) levels on angiographic severity of femoropopliteal lesions

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
K Yanaka ◽  
H Akahori ◽  
T Imanaka ◽  
K Miki ◽  
N Yoshihara ◽  
...  
Keyword(s):  
De Novo ◽  
Independent Predictor ◽  
Lesion Length ◽  
Peripheral Artery ◽  
Lipoprotein A ◽  
Class D ◽  
Artery Disease ◽  
Peripheral Arterial ◽  
The Impact ◽  
Severe Calcification

Abstract Background High lipoprotein(a) [Lp(a)] levels are a risk factor for peripheral artery disease (PAD). However, the association between Lp(a) levels and angiographic severity of PAD has not been systematically studied. Purpose The aim of this study was to assess the impact of Lp(a) levels on angiographic severity of femoropopliteal lesions in patients with PAD. Methods We retrospectively analyzed a single-center database including 108 patients (74±8 years, 69% male) who underwent endovascular therapy for de novo femoropopliteal lesions and measured Lp(a) levels before therapy between June 2016 and September 2019. Patients were divided into low Lp(a) [LP(a) <30 mg/dL; 77 patients] and high Lp(a) [LP(a) ≥30 mg/dL; 31 patients] groups. Trans-Atlantic Inter-Society Consensus (TASC) II classification, calcification [referring to peripheral arterial calcium scoring system (PACSS) classification] and lesion length were compared between the groups. Results Median Lp(a) was 16 (7–31) mg/dL.The prevalence of TASC II class D (13% vs 38%, P<0.01) and severe calcification (PACSS 4) (6% vs 23%, P=0.02) was significantly higher and lesion length was longer (123±88 mm vs 175±102 mm, P<0.01) in the high Lp(a) group than in the low Lp(a) group.(Table and Figure) In multivariate analysis, Lp(a)≥30 was an independent predictor for TASC II class D (HR=3.67, P=0.02) and PACSS 4 (HR=4.97, P=0.02) prevalence. Conclusion Lp(a) was associated with angiographic severity of femoropopliteal lesions in patients with PAD. Comparison of angiographic severity Funding Acknowledgement Type of funding source: None

Sign in / Sign up

Export Citation Format

Share Document