Notes

Enhancing Docking Energy for Short Proteins Employing Random Natrual enviroment.
Polyhydroxyalkanoates (PHAs) are a potential replacement for some petrochemical-based plastics. PHAs are polyesters synthesized and stored by various bacteria and archaea in their cytoplasm as water-insoluble inclusions. PHAs are usually produced when the microbes are cultured with nutrient-limiting concentrations of nitrogen, phosphorus, sulfur, or oxygen and excess carbon sources. Such fermentation conditions have been optimized by industry to reduce the cost of PHAs produced commercially. Industrially, these biodegradable polyesters are derived from microbial fermentation processes utilizing various carbon sources. One of the major constraints in scaling-up PHA production is the cost of the carbon source metabolized by the microorganisms. Hence, cheap and renewable carbon substrates are currently being investigated around the globe. Plant and animal oils have been demonstrated to be excellent carbon sources for high yield production of PHAs. Waste streams from oil mills or the used oils, which are even cheaper, are also used. This approach not only reduces the production cost for PHAs, but also makes a significant contribution toward the reduction of environmental pollution caused by the used oil. Advancements in the genetic and metabolic engineering of bacterial strains have enabled a more efficient utilization of various carbon sources, in achieving high PHA yields with specified monomer compositions. This review discusses recent developments in the biosynthesis and classification of various forms of PHAs produced using crude and waste oils from the oil palm and fish industries. The biodegradability of the PHAs produced from these oils will also be discussed. Copyright © 2020 Surendran, Lakshmanan, Chee, Sulaiman, Thuoc and Sudesh.Intestine-Liver-on-chip systems can be useful to predict oral drug administration and first-pass metabolism in vitro in order to partly replace the animal model. While organ-on-chip technology can count on sophisticated micro-physiological devices, the engineered organs still remain artificial surrogates of the native counterparts. find more Here, we used a bottom-up tissue engineering strategy to build-up physiologically functional 3D Human Intestine Model (3D-HIM) as well as 3D Liver-microtissues (HepG2-μTPs) in vitro and designed a microfluidic Intestine-Liver-On-Chip (InLiver-OC) to emulate first-pass mechanism occurring in vivo. Our results highlight the ethanol-induced 3D-HIM hyper-permeability and stromal injury, the intestinal prevention on the liver injury, as well as the synergic contribution of the two 3D tissue models on the release of metabolic enzymes after high amount of ethanol administration. Copyright © 2020 De Gregorio, Telesco, Corrado, Rosiello, Urciuolo, Netti and Imparato.Direct bioproduction of DHAA (dihydroartemisinic acid) rather than AA (artemisinic acid), as suggested by previous work would decrease the cost of semi-biosynthesis artemisinin by eliminating the step of initial hydrogenation of AA. The major challenge in microbial production of DHAA is how to efficiently manipulate consecutive key enzymes ADH1 (artemisinic alcohol dehydrogenase), DBR2 [artemisinic aldehyde Δ11(13) reductase] and ALDH1 (aldehyde dehydrogenase) to redirect metabolic flux and elevate the ratio of DHAA to AA (artemisinic acid). Herein, DHAA biosynthesis was achieved in Saccharomyces cerevisiae by introducing a series of heterologous enzymes ADS (amorpha-4,11-diene synthase), CYP71AV1 (amorphadiene oxidase), ADH1, DBR2 and ALDH1, obtaining initial DHAA/AA ratio at 2.53. The flux toward DHAA was enhanced by pairing fusion proteins DBR2-ADH1 and DBR2-ALDH1, leading to 1.75-fold increase in DHAA/AA ratio (to 6.97). Moreover, to promote the substrate preference of ALDH1 to dihydroartemisinic aldehyde (the intermediate for DHAA synthesis) over artemisinic aldehyde (the intermediate for AA synthesis), two rational engineering strategies, including downsizing the active pocket and enhancing the stability of enzyme/cofactor complex, were proposed to engineer ALDH1. It was found that the mutant H194R, which showed better stability of the enzyme/NAD+ complex, obtained the highest DHAA to AA ratio at 3.73 among all the mutations. Then the mutant H194R was incorporated into above rebuilt fusion proteins, resulting in the highest ratio of DHAA to AA (10.05). Subsequently, the highest DHAA reported titer of 1.70 g/L (DHAA/AA ratio of 9.84) was achieved through 5 L bioreactor fermentation. The study highlights the synergy of metabolic engineering and protein engineering in metabolic flux redirection to get the most efficient product to the chemical process, and simplified downstream conversion process. Copyright © 2020 Zeng, Yao, Wang, Xiao and Yuan.Amniotic membrane (AM) is considered an important medical device with many applications in regenerative medicine. The therapeutic properties of AM are due to its resistant extracellular matrix and to the large number of bioactive molecules released by its cells. An important goal that still remains to be achieved is the identification of cultural and preservation protocols able to maintain in time the membrane morphology and the biological properties of its cells. Recently, our research group demonstrated that progesterone (P4) is crucial in preventing the loss of the epithelial phenotype of amniotic epithelial cells in vitro. Followed by this premise, it has been evaluated whether P4 may also affect AM properties in a short-term culture. Results confirm that P4 preserves AM integrity and architecture with respect to untreated AM, which showed alterations in morphology. Transmission electron microscopy (TEM) analyses demonstrate that P4 also maintains unaltered cell-cell junctions, nuclear status, and intracellular organelles. On the contrary, an untreated AM experienced an extensive cell death and a strong reduction of immunomodulatory properties, measured in terms of anti-inflammatory cytokine expression and secretion. Overall, these results could open to new strategies to ameliorate the protocols for cryopreservation and tissue culture, which represent preliminary stages of AM application in regenerative medicine. Copyright © 2020 Canciello, Teti, Mazzotti, Falconi, Russo, Giordano and Barboni.
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