Yeast Metabolic Engineering for Biosynthesis of Caffeic Acid-Derived Phenethyl Ester and Phenethyl Amide.

Caffeic acid (CA)-derived phenethyl ester (CAPE) and phenethyl amide (CAPA) are extensively investigated bioactive compounds with therapeutic applications such as antioxidant, anti-inflammatory, and anticarcinogenic properties. To construct microbial cell factories for production of CAPE or CAPA is a promising option given the limitation of natural sources for product extraction and the environmental toxicity of the agents used in chemical synthesis. We reported the successful biosynthesis of caffeic acid in yeast previously. Here in this work, we further constructed the downstream synthetic pathways in yeast for biosynthesis of CAPE and CAPA. After combinatorial engineering of yeast chassis based on the rational pathway engineering method and library-based SCRaMbLE method, we finally obtained the optimal strains that respectively produced 417 µg/L CAPE and 1081 µg/L CAPA. Two screened gene targets of ΔHAM1 and ΔYJL028W were discovered to help improve the product synthesis capacity. This is the first report of the de novo synthesis of CAPA from glucose in an engineered yeast chassis. Future work on enzyme and chassis engineering will further support improving the microbial cell factories for the production of CA derivatives.

A composite of graphene oxide and iron oxide nanoparticles for targeted drug delivery of temozolomide.

A magnetic targeting nanoparticle based on graphene oxide-ferroferric oxide (GO-Fe3O4) was investigated as a potential drug delivery vehicle. The formation of GO/Fe3O4 hybrid material was confirmed by Fourier transform infrared spectroscopy, X-ray diffraction, scanning electron microscopy and transmission electron microscopy. The GO/Fe3O4 hybrid still shows a higher saturation magnetization of 58.42 emu/g after coating with graphene oxide. Drug loading and releasing experiments demonstrate the GO-Fe3O4 hybrid has a good loading capacity of (6.47±0.08) mg/mg for temozolomide and a satisfactory release under slightly acidic condition. The MTT assays of glioma C6 cells exhibits the GO-Fe3O4 hybrid does not display toxicity with the concentration ranged from 40 to 120 µg/mL in vitro, while the complex of temozolomide loaded on GO/Fe3O4 has a better inhibitory effect on the proliferation of rat glioma C6 cells. All results suggest the prepared GO/Fe3O4 has potential applications in targeted anticancer drug delivery.

Folate-modified Graphene Oxide as the Drug Delivery System to Load Temozolomide.

OBJECTIVE: The folate-modified graphene oxide (GO-FA), which had good stability and biocompatibility on rat glioma cells was successfully prepared. METHODS: The formation and composition of GO-FA were confirmed by Scanning Electron Microscope (SEM), Transmission Electron Microscope (TEM), Fourier Transform Infrared Spectrum (FT-IR), Raman spectra and X-ray Photoelectron Spectroscopy (XPS spectra). The cell experiment suggested good biocompatibility of GO-FA on rat glioma cells. RESULTS: The experiment of GO-FA loading with Temozolomide (TMZ) showed that the maximum drug loading of GO-FA was 8.05 ± 0.20 mg/mg, with the drug loading rate of 89.52 ± 0.19 %. When TMZ was released from the folate-modified graphene oxide loading with temozolomide (GO-FATMZ), its release behavior in vitro showed strong pH dependence and sustained release property. The growth of rat glioma cells can be effectively inhibited by GO-FA-TMZ, with the cell inhibition rate as high as 91.72 ± 0.13 % at the concentration of 600 µg/mL and time of 72 h. CONCLUSION: According to the above experimental results, this composite carrier has potential applications in drug delivery and cancer therapy.

Noble gas insertion compounds of hydrogenated and lithiated hyperhalogens.

Based on density functional theory (DFT) calculations, hydrogenated hyperhalogen HM(BO2)2, lithiated hyperhalogen LiM(BO2)2 (M = Cu, Ag, Au), and their compounds with xenon were studied. Different insertion sites of Xe resulted in various isomers. According to the natural population analysis, the Xe atom donated 0.12-0.77 electrons to HM(BO2)2 and 0.14-0.41 electrons to LiM(BO2)2 when they combined, leading to metastable charge-transfer compounds in most cases. The nature of bonding between xenon and HM(BO2)2/LiM(BO2)2 was found to be related to its location. Covalent bonds were formed when Xe bound with hydrogen atoms, as indicated by the large Wiberg bond indices of the Xe-H bonds. The same was true for most Xe-M bondings. When an Xe-O connection was formed, it was either an ionic or van der Waals force in nature depending on the specific structural feature of the isomer. A parallel study on hyperhalogen-supported Ar and Kr compounds indicated that they were not very stable and were less likely to exist at room temperature, which was in accordance with the high inertness of both Ar and Kr atoms.