Designing an <Emphasis Type="Italic">Escherichia coli</Emphasis> Strain for Phenylalanine Overproduction by Metabolic Engineering

The phenylalanine pathway flux is controlled by two types of regulators, those that are specific to the pathway, as well as by global regulators. In order to demonstrate the importance of these global regulators, we first removed the pathway-specific regulators using all possible combinations of gene knockouts and knockins. We found that genes like aroG ^fbr performed best individually as well as in combination with other genes, while other genes like tyrA and tyrR worked only in combination with other modifications. Knocking in the tktA gene under a tyrR promoter and knocking out pykF further increased phenylalanine production demonstrating that the supply of precursor via PEP and E4P is also a rate-limiting step. Finally, we tested the role of global regulators on this deregulated pathway and found that Fis overexpression helps in both enhancing and sustaining the flux through this pathway. This work opens up the possibility of using global regulators in synergy with pathway-specific modifications to enhance product yields.     

Design, synthesis and evaluation of novel 16-imidazolyl substituted steroidal derivatives possessing potent diversified pharmacological properties

As a part of our investigations into the structural-activity relationship studies of a novel class of medicinally active 16-substituted steroids, several new 16-imidazolyl substituted steroidal derivatives have been synthesized and pharmacologically evaluated in the current study. The new steroidal analogues 5, 6, 8, 9, 11 and 12 exhibited moderate cytotoxic effects in sixty cancer cell lines derived from nine cancers types. The imidazolyl substituted steroidal derivatives 6 (DPJ-RG-1241) and 7 (RB-401) were obtained as the powerful inhibitors of aromatase with IC50=0.18 μM and IC50=0.168 μM, respectively, approximately 1.2 and 1.4 times more potent in comparison to standard drug exemestane. The bis-quaternary steroids 13 and 14 displayed potent skeletal muscle relaxant properties. An affinity constant of 0.007 μM was observed for compound 14 on frog rectus abdominis muscle preparation and 13 displayed a very high anticholinesterase activity K(i)=25 nM, approximately 115-fold higher in comparison to standard drug galanthamine (K(i)=2.9 μM).     

Identification of miR414 and expression analysis of conserved miRNAs from Stevia rebaudiana

MicroRNAs (miRNAs) usually contain 19-24 nucleotides and have been identified as important eukaryotic gene regulators. Applications of various computational approaches have simplified the task by predicting miRNAs from available sequence data sources. In this study, we identified a conserved miR414 from a computational analysis of EST sequence data available from Stevia rebaudiana. In addition, we also identified six conserved miRNAs namely miR169, miR319, miR414, miR164, miR167 and miR398 using stem-loop RT-PCR analysis. Hence, miR414 was commonly identified using both methods. The expression analysis of these miRNAs documented their roles in growth and development of Stevia. Furthermore, the detected miRNAs were found to target genes involved in plant growth, development, metabolism and signal transduction. This is the first study reporting these conserved miRNAs and their expression in Stevia.     

Genetic Engineering: A Possible Strategy for Protein–Energy Malnutrition Regulation

Protein–energy malnutrition (PEM) has adversely affected the generations of developing countries. It is a syndrome that in severity causes death. PEM generally affects infants of 1–5 age group. This manifestation is maintained till adulthood in the form of poor brain and body development. The developing nations are continuously making an effort to curb PEM. However, it is still a prime concern as it was in its early years of occurrence. Transgenic crops with high protein and enhanced nutrient content have been successfully developed. Present article reviews the studies documenting genetic engineering-mediated improvement in the pulses, cereals, legumes, fruits and other crop plants in terms of nutritional value, stress tolerance, longevity and productivity. Such genetically engineered crops can be used as a possible remedial tool to eradicate PEM.     

Antimicrobial studies,synthesis and characterization of novel 1-nitro-10H-phenothiazine bearing sulfone/nucleoside moieties

The current research article involves one pot synthesis of novel substituted 1-nitro-10H-phenothiazines via Smiles rearrangement. These substituted phenothiazines undergo oxidation to yield 10H-phenothiazine-5,5-dioxides (sulfones) while on treatment with β-D-ribofuranose-1-acetate-2,3,5-tribenzoate yield ribofuranosides. These compounds were screened for their antimicrobial vitalities (in vitro) against selected strains of bacteria and fungi. The characterization of synthesized compounds was done by elemental and spectral studies.