Performance of coimmobilized yeast and amyloglucosidase in a fluidized bed reactor for fuel ethanol production

Applied Biochemistry and Biotechnology - The performance of coimmobilizedSaccharomyces cerevisiae and amyloglucosidase (AG) was evaluated in a fluidized-bed reactor. Soluble starch and yeast...     

Performance of chloroperoxidase stabilization in mesoporous sol-gel glass using In situ glucose oxidase peroxide generation

A unique mesoporous sol-gel glass possessing a highly ordered porous structure (with three pore sizes of about 50, 150, and 200 Å diameter) was used as a support material for immobilization of the enzyme chloroperoxidase (CPO). CPO was bound onto the glass via a bifunctional ligand, trimethoxysilylpropanal. In situ production of the cosubstrate, H₂O₂, was achieved using glucose oxidase. Solvent stability in acetonitrile mixtures was enhanced when a pore size larger than the size of CPO was used (i.e., 200) Å From these results, it appears that the glass-enzyme complex developed through the present work can be used as high-performance biocatalysts for various chemical-processing applications, particularly in harsh conditions.     

Mechanism-of-action determination of GMP synthase inhibitors and target validation in Candida albicans and Aspergillus fumigatus

Mechanism-of-action (MOA) studies of bioactive compounds are fundamental to drug discovery. However, in vitro studies alone may not recapitulate a compound's MOA in whole cells. Here, we apply a chemogenomics approach in Candida albicans to evaluate compounds affecting purine metabolism. They include the IMP dehydrogenase inhibitors mycophenolic acid and mizoribine and the previously reported GMP synthase inhibitors acivicin and 6-diazo-5-oxo-L-norleucine (DON). We report important aspects of their whole-cell activity, including their primary target, off-target activity, and drug metabolism. Further, we describe ECC1385, an inhibitor of GMP synthase, and provide biochemical and genetic evidence supporting its MOA to be distinct from acivicin or DON. Importantly, GMP synthase activity is conditionally essential in C. albicans and Aspergillus fumigatus and is required for virulence of both pathogens, thus constituting an unexpected antifungal target.     

Potential Symmetries and Associated Conservation Laws with Application to Wave Equations

It has been shown that one can generate a class of nontrivial conservation laws for second-order partial differential equations using some recent results dealing with the action of any Lie–Bäcklund symmetry generator of the equivalentfirst-order system on the respective conservation law. These conservedvectors are nonlocal as they are constructed from associatednonlocal symmetries of the partial differential equation. The method canbe successfully extended to association with genuine nonlocal(potential) symmetries. However, it usually involves solving moredifficult systems of partial differential equations which may not alwaysbe easy to uncouple.     

Controlled incorporation of deuterium into bacterial cellulose

Isotopic enrichment has been widely used for investigating the structural and dynamic properties of biomacromolecules to provide information that cannot be carried out with molecules composed of natural abundance isotopes. A media formulation for controlled incorporation of deuterium in bacterial cellulose synthesized by Gluconacetobacter xylinus subsp. sucrofermentans is reported. The purified cellulose was characterized using Fourier Transform Infra-Red spectrophotometry and mass spectrometry which revealed that the level of deuterium incorporation in the perdeuterated cellulose was greater than 90 %. Small-angle neutron scattering analysis demonstrated that the overall structure of the cellulose was unaffected by the substitution of deuterium for hydrogen. In addition, by varying the amount of D-glycerol in the media it was possible to vary the scattering length density of the deuterated cellulose. A large disk model was used to fit the curves of bacterial cellulose grown using 0 and 100 % D-Glycerol yielding a lower bound to the disk radii, R _min = 1,132 ± 6 and 1,154 ± 3 Å and disk thickness, T = 128 ± 1 and 83 ± 1 Å for the protiated and deuterated forms of the bacterial cellulose, respectively. This agrees well with the scanning electron microscopy analysis which revealed stacked sheets in the cellulose pellicles. Controlled incorporation of deuterium into cellulose will enable new types of experiments using techniques such as neutron scattering to reveal information about the structure and dynamics of cellulose and its interactions with proteins and other (bio) polymers.     

(±)‐7‐Oxo‐1,2,3,4,4a,5,6,7‐octa­hydro­naphthalene‐1‐acetic acid: catemeric hydrogen bonding and diastereomeric disorder in a bicyclic unsaturated ɛ‐keto acid

The 68.5:31.5 mixture of diastereoisomers obtained in the synthesis of the title compound, C₁₂H₁₆O₃, yielded sharply melting crystals containing the same ratio of epimers, in a disordered crystallographic arrangement. The disorder resides almost entirely in the carboxy­methyl side chain, but places the two sets of carboxyl O atoms at nearly identical paired spatial positions. Neither component displays significant carboxyl disorder, and the mol­ecules aggregate as hydrogen‐bonded carboxyl‐to‐ketone catemers [O⋯O = 2.673 (4) Å and O—H⋯O = 158°] having glide‐related components, with centro­symmetrically related pairs of chains following axes perpendicular to b. Close intermolecular C—H⋯O contacts exist for both the ketone and the carboxyl group. The energetics of the epimers and of their crystallization mode are discussed.     

Forensic performance of Investigator DIPplex indels genotyping kit in native,immigrant, and admixed populations in South Africa

The utilization of binary markers in human individual identification is gaining ground in forensic genetics. We analyzed the polymorphisms from the first commercial indel kit Investigator DIPplex (Qiagen) in 512 individuals from Afrikaner, Indian, admixed Cape Colored, and the native Bantu Xhosa and Zulu origin in South Africa and evaluated forensic and population genetics parameters for their forensic application in South Africa. The levels of genetic diversity in population and forensic parameters in South Africa are similar to other published data, with lower diversity values for the native Bantu. Departures from Hardy–Weinberg expectations were observed in HLD97 in Indians, Admixed and Bantus, along with 6.83% null homozygotes in the Bantu populations. Sequencing of the flanking regions showed a previously reported transition G>A in rs17245568. Strong population structure was detected with Fst, AMOVA, and the Bayesian unsupervised clustering method in STRUCTURE. Therefore we evaluated the efficiency of individual assignments to population groups using the ancestral membership proportions from STRUCTURE and the Bayesian classification algorithm in Snipper App Suite. Both methods showed low cross‐assignment error (0–4%) between Bantus and either Afrikaners or Indians. The differentiation between populations seems to be driven by four loci under positive selection pressure. Based on these results, we draw recommendations for the application of this kit in SA.     

Dual Targeting of MDM4 and FTH1 by MMRi71 for Induced Protein Degradation and p53-Independent Apoptosis in Leukemia Cells

MDM2 and MDM4 are cancer drug targets validated in multiple models for p53-based cancer therapies. The RING domains of MDM2 and non-p53-binder MDM2 splice isoforms form RING domain heterodimer polyubiquitin E3 ligases with MDM4, which regulate p53 stability in vivo and promote tumorigenesis independent of p53. Despite the importance of the MDM2 RING domain in p53 regulation and cancer development, small molecule inhibitors targeting the E3 ligase activity of MDM2-MDM4 are poorly explored. Here, we describe the synthesis and characterization of quinolinol derivatives for the identification of analogs that are capable of targeting the MDM2-MDM4 heterodimer E3 ligase and inducing apoptosis in cells. The structure-activity-relationship (SAR) study identified structural moieties critical for the inhibitory effects toward MDM2-MDM4 E3 ligase, the targeted degradation of MDM4 and FTH1 in cells, and anti-proliferation activity. Lead optimization led to the development of compound MMRi71 with improved activity. In addition to accumulating p53 proteins in wt-p53 bearing cancer cells as expected of any MDM2 inhibitors, MMRi71 effectively kills p53-null leukemia cells, an activity that conventional MDM2-p53 disrupting inhibitors lack. This study provides a prototype structure for developing MDM4/FTH1 dual-targeting inhibitors as potential cancer therapeutics.     

Deuterium incorporation into cellulose: a mini-review of biological and chemical methods

Cellulose - Isotopic enrichment offers structural insights that are not easily accessible with natural abundance isotopic composition. Deuterated cellulose has attracted considerable attention in...     

Effect of temperature on biofiltration of nitric oxide

Applied Biochemistry and Biotechnology -