Computational Analysis for Physicochemical Properties of Compounds in Senna auriculata Leaves Methanolic Extract to have Antidiabetic Potentials and their Molecular Interaction with α-amylase

Aims: Diabetes mellitus (DM) is chronic disorder well known for increased glucose level in blood. This disease can be controlled by inhibiting the enzyme (e.g., α-amylase) involve in carbohydrate hydrolysis. Senna auriculata leaves methanolic extract (SALME) have potential antidiabetic properties and it was also found to be safe in preclinical studies. In this study the aim was to explore the molecular interactions of α-amylase and bioactive compounds in SALME and their physicochemical properties. Methodology: Computational approach such as molecular docking and physicochemical analysis prediction was applied to understand the antidiabetic potential of natural compounds present in SALME. Results: The results showed from physicochemical analysis that out of 11 only 7 compounds are having drug like properties which are orally and intestinally better bioavailable. Furthermore, molecular docking analysis explained that three compounds (C3, C4, and C7) have lower binding energy, ΔG (-8, -9.1, -9.5 kcal/mol) and better binding affinity, Ki (7.31 x 105, 4.68 x 106, and 9.2 x 106 M-1, respectively) than the acarbose ΔG (-7.8 kcal/mol) and Ki (6.18 x 105 M-1), a well-known FDA approved medication for DM. The study also explained the binding pattern that the catalytic residue such as Asp197, Glu233 and Asp300 are involved in stabilizing the natural compounds with in the catalytic active site of target enzyme. Conclusions: From the results it has been concluded that these three compounds found in SALME have better inhibitory potential for α-amylase in comparison with acarbose. Further validation of the findings is required through molecular dynamics simulation, ADME-T study, and in-vitro enzyme inhibition by the purified compounds.

Transcriptomics Analysis of Primordium Formation in Pleurotus eryngii

Primordium formation is an important stage preceding the growth and development of the Pleurotus eryngii fruiting body. However, the molecular mechanisms underlying primordium formation remain unclear. In the present study, comparative transcriptomics was performed between mature mycelia and primordium to analyze the transcriptional properties during primordium formation in P. eryngii. A total of 19,655 differentially expressed genes (10,718 upregulated genes and 8937 downregulated genes) were identified. These differentially expressed genes were involved in cell wall degradation, carbohydrate hydrolysis, light perception, and cAMP signal transduction. These results aid further understanding of the transcriptional changes and the molecular processes underlying primordium formation and differentiation, which may lay the foundation for improving the cultivation and quality control of P. eryngii.

Zetaproteobacteria Pan-Genome Reveals Candidate Gene Cluster for Twisted Stalk Biosynthesis and Export

Twisted stalks are morphologically unique bacterial extracellular organo-metallic structures containing Fe(III) oxyhydroxides that are produced by microaerophilic Fe(II)-oxidizers belonging to the Betaproteobacteria and Zetaproteobacteria. Understanding the underlying genetic and physiological mechanisms of stalk formation is of great interest based on their potential as novel biogenic nanomaterials and their relevance as putative biomarkers for microbial Fe(II) oxidation on ancient Earth. Despite the recognition of these special biominerals for over 150 years, the genetic foundation for the stalk phenotype has remained unresolved. Here we present a candidate gene cluster for the biosynthesis and secretion of the stalk organic matrix that we identified with a trait-based analyses of a pan-genome comprising 16 Zetaproteobacteria isolate genomes. The “stalk formation in Zetaproteobacteria” (sfz) cluster comprises six genes (sfz1-sfz6), of which sfz1 and sfz2 were predicted with functions in exopolysaccharide synthesis, regulation, and export, sfz4 and sfz6 with functions in cell wall synthesis manipulation and carbohydrate hydrolysis, and sfz3 and sfz5 with unknown functions. The stalk-forming Betaproteobacteria Ferriphaselus R-1 and OYT-1, as well as dread-forming Zetaproteobacteria Mariprofundus aestuarium CP-5 and Mariprofundus ferrinatatus CP-8 contain distant sfz gene homologs, whereas stalk-less Zetaproteobacteria and Betaproteobacteria lack the entire gene cluster. Our pan-genome analysis further revealed a significant enrichment of clusters of orthologous groups (COGs) across all Zetaproteobacteria isolate genomes that are associated with the regulation of a switch between sessile and motile growth controlled by the intracellular signaling molecule c-di-GMP. Potential interactions between stalk-former unique transcription factor genes, sfz genes, and c-di-GMP point toward a c-di-GMP regulated surface attachment function of stalks during sessile growth.

Zetaproteobacteria pan-genome reveals candidate gene cluster for twisted stalk biosynthesis and export

Twisted stalks are morphologically unique bacterial extracellular organo-metallic structures containing Fe(III) oxyhydroxides that are produced by microaerophilic Fe(II)-oxidizers belonging to the Betaproteobacteria and Zetaproteobacteria. Understanding the underlying genetic and physiological mechanisms of stalk formation is of great interest based on their potential as novel biogenic nanomaterials and their relevance as putative biomarkers for microbial Fe(II) oxidation on ancient Earth. Despite the recognition of these special biominerals for over 150 years, the genetic foundation for the stalk phenotype has remained unresolved. Here we present a candidate gene cluster for the biosynthesis and secretion of the stalk organic matrix that we identified with a trait-based analyses of a pan-genome comprising 16 Zetaproteobacteria isolate genomes. The “stalk formation in Zetaproteobacteria” (sfz) cluster comprises six genes (sfz1-sfz6), of which sfz1 and sfz2 were predicted with functions in exopolysaccharide synthesis, regulation, and export, sfz4 and sfz6 with functions in cell wall synthesis manipulation and carbohydrate hydrolysis, and sfz3 and sfz5 with unknown functions. The stalk-forming Betaproteobacteria Ferriphaselus R-1 and OYT-1, as well as dread-forming Zetaproteobacteria Mariprofundus aestuarium CP-5 and Mariprofundus ferrinatatus CP-8 contain distant sfz gene homologues, whereas stalk-less Zetaproteobacteria and Betaproteobacteria lack the entire gene cluster. Our pan-genome analysis further revealed a significant enrichment of clusters of orthologous groups (COGs) across all Zetaproteobacteria isolate genomes that are associated with the regulation of a switch between sessile and motile growth controlled by the intracellular signaling molecule c-di-GMP. Potential interactions between stalk-former unique transcription factor genes, sfz genes, and c-di-GMP point towards a c-di-GMP regulated surface attachment function of stalks during sessile growth.

Study of Carbohydrate Hydrolysis From Arracacha Roots (Arracacia Xanthorriza Bancroft) to Produce Fermentable Sugars

In Colombia, approximately 855 840 tons of arracacha are produced each year. The unsalable postharvest arracacha root (Arracacia xanthorriza Bancroft) is not commercialized, mainly due to mechanical damage or small and misshapen roots. In this work, dry samples were characterized and subjected to two treatments: one using thermal hydrolysis, applying saturated steam at pressures of 0,1034 MPa, 0,2068 MPa, and 0,4137 MPa; and another one using hydrolysis with sulfuric acid in concentrations between 0,252,00 M. Then, the cake resulting from the hydrolysis and filtration process was enzymatically hydrolyzed (Liquozyme SC DS, Novozymes) at 1,5, 5 and 10 KNU/g (pH 6, 80 _C, 2 h). Fermentation inhibitors (acetic acid and furfural) were evaluated in the best pretreatment. The results showed that the treatment with sulfuric acid at 1,00 M (2 h) has high yields in reducing sugars added to enzymatic hydrolysis. The maximum level of fermentable carbohydrates per gram of dry sample (1,04 g/g) was also reached. Regarding the fermentation inhibitors of the reducing sugar, a higher concentration of acetic acid was found with a lower furfural content. Therefore, arracacha discards are a promising raw material to increase the supply of bioethanol.

Fractionation of Waste MDF by Steam Refining

In view of the expected increase in available waste medium-density fiberboard (MDF) and the current insufficient and unsatisfactory disposal capacities, efficient ways of recycling the waste material need to be developed. In this study, the potential of steam refining as a method to hydrolyze the resins, isolate fibers, and obtain a hemicellulose-rich extract available for further utilization in the context of a biorefinery was assessed. Two different MDF waste samples, as well as poplar (Populus spp.) and spruce (Picea spp.) wood chips for benchmarking, were treated over a severity range from 2.47 to 3.95. The separated fiber and extract fractions were analyzed with regard to yield, content of carbohydrates, acids, degradation products, and nitrogen. A fiber fraction of more than 70% yield and an extract containing up to 30% of carbohydrates for further processing can be gained by steam-refining waste MDF. At low severities, most of the nitrogen-based compounds are solubilized. Increasing the severity leads to a decrease in nitrogen in the extract as the nitrogen compounds are converted into volatiles. A non-hydrolysable resin residue remains on the fibers, independent of the treatment severity. In comparison to the benchmark samples, the extract fraction of waste MDF shows a high pH of 8 and high amounts of acetic and formic acid. The generation of furfural and 5-hydroxymethylfurfural (5-HMF) on the other hand is suppressed. Distinct differences in carbohydrate hydrolysis behavior between waste MDF and conventional wood can be observed. Especially, the mannose-containing constituents seem to be resistant to hydrolysis reactions in the milieu created in MDF fractionation.

Discovery of Novel α-Amylase Inhibitors as Type Two Diabetes Mellitus Therapy through Fragment-Based Drug Design

Diabetes is one of the top causes of death in the world, with 425 million sufferers reported in 2017. About 90% of diabetics suffer from Type 2 Diabetes Mellitus (T2DM). Recent studies show that inhibiting the α-amylase enzyme can significantly decrease the postprandial blood glucose levels through blocking carbohydrate hydrolysis. Therefore, it can be a promising strategy for T2DM treatment. This research was aimed to find the new potential inhibitor for the α-amylase from lead-like compounds Molecular Operating Environment (MOE) database through fragment-based drug design, combining with structure-based pharmacophore design method to obtain new drug candidate for T2DM. There were 653,214 lead-like compounds which were obtained from MOE database and screened based on the Astex Rules of Three along with toxicity filter to gain lead-like fragments. The filtered fragments were docked into the binding site of the α-amylase utilizing MOE 2014.09 software. Potential lead-like fragments were grown to generate 25,600 new ligands by utilizing DataWarrior v5.0.0 software, based on the Lipinski’s Rule of Five and toxicity filter. Molecular docking simu-lation and pharmacological test was performed on the ligand libraries to acquire the best ligand, namely BGOJI which were chosen according to the lowest ΔG binding score, RMSD value < 2, good molecular interaction, ADME/T test result.

Effect of Pre-Corrected pH on the Carbohydrate Hydrolysis of Bamboo during Hydrothermal Pretreatment

To confirm the prospects for application of pre-corrected pH hydrothermal pretreatment in biorefineries, the effects of pH on the dissolution and degradation efficiency of carbohydrates were studied. The species composition of the hydrolysate was analyzed using high efficiency anion exchange chromatography and UV spectroscopy. The result showed that the greatest balance between the residual solid and total dissolved solids was obtained at pH 4 and 170 °C. Maximum recovery rates of cellulose and lignin were as expected, whereas hemicellulose had the least recovery rate. The hemicellulose extraction rate was 42.19%, and the oligomer form accounted for 93.39% of the product. The physicochemical properties of bamboo with or without pretreatment was characterized. Compared with the traditional hydrothermal pretreatment, the new pretreatment bamboo has higher fiber crystallinity and thermal stability. In the pretreatment process, the fracture of β-aryl ether bond was inhibited and the structural dissociation of lignin was reduced. The physicochemical properties of bamboo was protected while the hemicellulose was extracted efficiently. It provides theoretical support for the efficient utilization of all components of woody biomass.