scholarly journals Engineering of Bacillus subtilis for Enhanced Total Synthesis of Folic Acid

2005 ◽  
Vol 71 (11) ◽  
pp. 7122-7129 ◽  
Author(s):  
T. Zhu ◽  
Z. Pan ◽  
N. Domagalski ◽  
R. Koepsel ◽  
M. M. Ataai ◽  
...  
Keyword(s):  
Bacillus Subtilis ◽  
Folic Acid ◽  
Total Synthesis ◽  
Pyruvate Kinase ◽  
Flux Analysis ◽  
Single Mutation ◽  
Acid Yield ◽  
Mutation Strategies ◽  
B Vitamin ◽  
Acid Precursor

ABSTRACT We investigated whether the yield of the B vitamin folic acid could be elevated in Bacillus subtilis. Strategies for increasing the folic acid yield were investigated by employing computer-aided flux analysis and mutation. Controlling the activity of the enzyme pyruvate kinase by placing it under inducible control was one strategy devised to elevate yield while insuring that a rapid growth rate results. Other single mutation strategies included amplifying the expression of the genes in the folate operon and overexpressing the Escherichia coli aroH gene, which encodes 2-dehydro-3-deoxyphosphoheptonate aldolase. The latter could conceivably elevate the abundance of the folic acid precursor, para-aminobenzoic acid. Strains that combined two or more mutations were also constructed. Overall, a strain possessing inducible pyruvate kinase, overexpressed aroH, and increased transcription and translation of genes from the folic operon exhibited the best yield. The yield was eightfold higher than that displayed by the parent B. subtilis 168 strain.

13C NMR Evidence for Pyruvate Kinase Flux Attenuation Underlying Suppressed Acid Formation in Bacillus subtilis

2000 ◽  
Vol 16 (2) ◽  
pp. 169-175 ◽  
Author(s):  
C. Phalakornkule ◽  
B. Fry ◽  
T. Zhu ◽  
R. Kopesel ◽  
M.M. Ataai ◽  
...  
Keyword(s):  
Bacillus Subtilis ◽  
Pyruvate Kinase ◽  
13C Nmr ◽  
Acid Formation

scholarly journals Adaptive Unified Differential Evolution for Clustering

2018 ◽  
Vol 12 (1) ◽  
pp. 53
Author(s):  
Maulida Ayu Fitriani ◽  
Aina Musdholifah ◽  
Sri Hartati
Keyword(s):  
Differential Evolution ◽  
Fitness Function ◽  
Single Mutation ◽  
Clustering Methods ◽  
Mutation Strategy ◽  
Clustering Quality ◽  
Silhouette Index ◽  
Mutation Strategies ◽  
Time Required

Various clustering methods to obtain optimal information continues to evolve one of its development is Evolutionary Algorithm (EA). Adaptive Unified Differential Evolution (AuDE), is the development of Differential Evolution (DE) which is one of the EA techniques. AuDE has self adaptive scale factor control parameters (F) and crossover-rate (Cr).. It also has a single mutation strategy that represents the most commonly used standard mutation strategies from previous studies.The AuDE clustering method was tested using 4 datasets. Silhouette Index and CS Measure is a fitness function used as a measure of the quality of clustering results. The quality of the AuDE clustering results is then compared against the quality of clustering results using the DE method.The results show that the AuDE mutation strategy can expand the cluster central search produced by ED so that better clustering quality can be obtained. The comparison of the quality of AuDE and DE using Silhoutte Index is 1:0.816, whereas the use of CS Measure shows a comparison of 0.565:1. The execution time required AuDE shows better but Number significant results, aimed at the comparison of Silhoutte Index usage of 0.99:1 , Whereas on the use of CS Measure obtained the comparison of 0.184:1.

scholarly journals Developmental Impairments in a Rat Model of Methyl Donor Deficiency: Effects of a Late Maternal Supplementation with Folic Acid

2019 ◽  
Vol 20 (4) ◽  
pp. 973 ◽  
Author(s):  
Andréa Geoffroy ◽  
Lynda Saber-Cherif ◽  
Grégory Pourié ◽  
Déborah Helle ◽  
Rémy Umoret ◽  
...  
Keyword(s):  
Folic Acid ◽  
Folic Acid Supplementation ◽  
Vitamin Deficiency ◽  
Folate Supplementation ◽  
Control Of Gene Expression ◽  
Methyl Donors ◽  
Maternal Supplementation ◽  
One Carbon Metabolism ◽  
The One ◽  
B Vitamin

Vitamins B9 (folate) and B12 act as methyl donors in the one-carbon metabolism which influences epigenetic mechanisms. We previously showed that an embryofetal deficiency of vitamins B9 and B12 in the rat increased brain expression of let-7a and miR-34a microRNAs involved in the developmental control of gene expression. This was reversed by the maternal supply with folic acid (3 mg/kg/day) during the last third of gestation, resulting in a significant reduction of associated birth defects. Since the postnatal brain is subject to intensive developmental processes, we tested whether further folate supplementation during lactation could bring additional benefits. Vitamin deficiency resulted in weaned pups (21 days) in growth retardation, delayed ossification, brain atrophy and cognitive deficits, along with unchanged brain level of let-7a and decreased expression of miR-34a and miR-23a. Whereas maternal folic acid supplementation helped restore the levels of affected microRNAs, it led to a reduction of structural and functional defects taking place during the perinatal/postnatal periods, such as learning/memory capacities. Our data suggest that a gestational B-vitamin deficiency could affect the temporal control of the microRNA regulation required for normal development. Moreover, they also point out that the continuation of folate supplementation after birth may help to ameliorate neurological symptoms commonly associated with developmental deficiencies in folate and B12.

scholarly journals Plasma Vitamin B6 Vitamers before and after Oral Vitamin B6 Treatment: A Randomized Placebo-controlled Study

2003 ◽  
Vol 49 (1) ◽  
pp. 155-161 ◽  
Author(s):  
Mustafa Vakur Bor ◽  
Helga Refsum ◽  
Marianne R Bisp ◽  
Øyvind Bleie ◽  
Jorn Schneede ◽  
...  
Keyword(s):  
Folic Acid ◽  
Vitamin B12 ◽  
Vitamin B6 ◽  
Oral Treatment ◽  
Prolonged Treatment ◽  
Controlled Study ◽  
Plasma Vitamin ◽  
Additional Increase ◽  
Before And After ◽  
B Vitamin

Abstract Background: Vitamin B6 has attracted renewed interest because of its role in homocysteine metabolism and its possible relation to cardiovascular risk. We examined the plasma B6 vitamers, pyridoxal 5′-phosphate (PLP), pyridoxal (PL), pyridoxine (PN), and 4-pyridoxic acid (4-PA) before and after vitamin B6 supplementation. Methods: Patients (n = 90; age range, 38–80 years) undergoing coronary angiography (part of the homocysteine-lowering Western Norway B-Vitamin Intervention Trial) were allocated to the following daily oral treatment groups: (A), vitamin B12 (0.4 mg), folic acid (0.8 mg), and vitamin B6 (40 mg); (B), vitamin B12 and folic acid; (C), vitamin B6; or (D), placebo. EDTA blood was obtained before treatment and 3, 14, 28, and 84 days thereafter. Results: Before treatment, PLP (range, 5–111 nmol/L) and 4-PA (6–93 nmol/L) were the predominant B6 vitamers identified in plasma. During the 84-day study period, the intraindividual variation (CV) in patients not treated with vitamin B6 (groups B and D) was 45% for PLP and 67% for 4-PA. Three days after the start of treatment, the increases in concentration were ∼10-, 50-, and 100-fold for PLP, 4-PA, and PL, respectively. No significant additional increase was observed at the later time points. The PLP concentration correlated to the concentrations of 4-PA and PL before treatment, but not after treatment. The PL concentration correlated with 4-PA before and after treatment. Conclusions: Vitamin B6 treatment has an immediate effect on the concentrations and the forms of B6 vitamers present in plasma, and the changes remain the same during prolonged treatment. Our results suggest that the B6 vitamers in plasma reflect vitamin B6 intake.

scholarly journals YtsJ Has the Major Physiological Role of the Four Paralogous Malic Enzyme Isoforms in Bacillus subtilis

2006 ◽  
Vol 188 (13) ◽  
pp. 4727-4736 ◽  
Author(s):  
Guillaume Lerondel ◽  
Thierry Doan ◽  
Nicola Zamboni ◽  
Uwe Sauer ◽  
Stéphane Aymerich
Keyword(s):  
Enzyme Activity ◽  
Bacillus Subtilis ◽  
Malic Enzyme ◽  
Metabolic Flux ◽  
Physiological Role ◽  
Extreme Case ◽  
Growth Defect ◽  
Flux Analysis ◽  
Malic Enzyme Activity

ABSTRACT The Bacillus subtilis genome contains several sets of paralogs. An extreme case is the four putative malic enzyme genes maeA, malS, ytsJ, and mleA. maeA was demonstrated to encode malic enzyme activity, to be inducible by malate, but also to be dispensable for growth on malate. We report systematic experiments to test whether these four genes ensure backup or cover different functions. Analysis of single- and multiple-mutant strains demonstrated that ytsJ has a major physiological role in malate utilization for which none of the other three genes could compensate. In contrast, maeA, malS, and mleA had distinct roles in malate utilization for which they could compensate one another. The four proteins exhibited malic enzyme activity; MalS, MleA, and MaeA exhibited 4- to 90-fold higher activities with NAD+ than with NADP+. YtsJ activity, in contrast, was 70-fold higher with NADP+ than with NAD+, with Km values of 0.055 and 2.8 mM, respectively. lacZ fusions revealed strong transcription of ytsJ, twofold higher in malate than in glucose medium, but weak transcription of malS and mleA. In contrast, mleA was strongly transcribed in complex medium. Metabolic flux analysis confirmed the major role of YtsJ in malate-to-pyruvate interconversion. While overexpression of the NADP-dependent Escherichia coli malic enzyme MaeB did not suppress the growth defect of a ytsJ mutant on malate, overexpression of the transhydrogenase UdhA from E. coli partially suppressed it. These results suggest an additional physiological role of YtsJ beyond that of malate-to-pyruvate conversion.

Homocysteine, folic acid and vitamin B12 in relation to pre- and postnatal health aspects

2005 ◽  
Vol 43 (10) ◽  
Author(s):  
Rima Obeid ◽  
Wolfgang Herrmann
Keyword(s):  
Folic Acid ◽  
Vitamin B12 ◽  
Pregnancy Outcomes ◽  
Pregnancy Complications ◽  
Plasma Homocysteine ◽  
Vitamin B ◽  
Total Plasma ◽  
Vitamin Status ◽  
B Vitamin ◽  
Early Abortion

AbstractStudies linking hyperhomocysteinemia (HHCY) and B-vitamin deficiency to some health aspects in children have been accumulating. Low B-vitamin status inearly life, even as early as the time of conception, may endanger the potential for new life and may negatively influence the health of the offspring. Early abortion, pregnancy complications and poor pregnancy outcomes have been linked to elevated concentrations of total plasma homocysteine (tHcy) and low folate or vitamin B

13C-metabolic flux analysis in heterologous cellulase production by Bacillus subtilis genome-reduced strain

2014 ◽  
Vol 179 ◽  
pp. 42-49 ◽  
Author(s):  
Yoshihiro Toya ◽  
Takashi Hirasawa ◽  
Takuya Morimoto ◽  
Kenta Masuda ◽  
Yasushi Kageyama ◽  
...  
Keyword(s):  
Bacillus Subtilis ◽  
Metabolic Flux Analysis ◽  
Metabolic Flux ◽  
Cellulase Production ◽  
Flux Analysis ◽  
13C Metabolic Flux Analysis ◽  
Subtilis Genome
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