Development of a continuous fermentation process for the production of recombinant uricase enzyme by Pichia pastoris.

Recent studies in the biopharmaceutical industry have shown an increase in the productivity and production efficiency of recombinant proteins by continuous culture. In this research, a new upstream fermentation process was developed for the production of recombinant uricase in the methylotrophic yeast Pichia pastoris. Expression of recombinant protein in this system is under the control of the AOX1 promoter and therefore requires methanol as an inducing agent and carbon/energy source. Considering the biphasic growth characteristics of conventional fed-batch fermentation, physical separation of the growth and induction stages for better control of the continuous fermentation process resulted in higher dry-cell weight (DCW) and enhanced recombinant urate oxidase activity. The DCW and recombinant uricase activity enzyme for fed-batch fermentation were 79 g/L and 6.8 u/mL. During the continuous process, in the growth fermenter at a constant dilution rate of 0.025 h-1 , DCW increased to 88.39 g/L. In the induction fermenter, at methanol feeding rates of 30, 60, and 80 mL/h, a recombinant uricase activity was 4.13, 7.2, and 0 u/mL, respectively. The optimum methanol feeding regime in continuous fermentation resulted in a 4.5-fold improvement in productivity compared with fed-batch fermentation from 0.04 u/mL/h (0.0017 mg/mL/h) to 0.18 u/mL/h (0.0078 mg/mL/h).

The Prominent Role of Protein-Based Delivery Systems on the Development of Cancer Treatment.

Nanotherapeutics has the potential of providing limitless opportunities in the area of drug and gene delivery for treatment of cancer. Although the path toward commercialization of nanoparticulate oncology drugs is long and carries significant risks, there is still considerable excitement for utilizing nanoparticle technologies in cancer drug development. Recently, there has been a significant growth in the number of nanoparticle delivery systems, used in clinical trials. Several incorporations have been established between pharmaceutical and nanotechnology companies striving to understand, develop and utilize effective interactions between nanomaterials and biological systems for cancer treatment by means of colloidal delivery systems. Protein-based nanoparticles, with one already approved and several under-development products in the commercial market, are of the pioneers of the successful employment of nanoparticulate systems in improving the cancer treatment techniques. The main reason behind the widely tendency to the usage of protein-based systems is their possibility of functionalization, biocompatibility, nonimmunogenicity, and high loading capacity for both hydrophobic and hydrophilic therapeutics. The aim of this review is to provide a comprehensive overview on the most recent findings in the area of utilization of protein-based nanoparticles for delivery of anticancer agents, as well as interpretation of the challenges encountered in the field.

Biodegradation of low-density polyethylene (LDPE) by isolated fungi in solid waste medium.

In this study, biodegradation of low-density polyethylene (LDPE) by isolated landfill-source fungi was evaluated in a controlled solid waste medium. The fungi, including Aspergillus fumigatus, Aspergillus terreus and Fusarium solani, were isolated from samples taken from an aerobic aged municipal landfill in Tehran. These fungi could degrade LDPE via the formation of a biofilm in a submerged medium. In the sterilized solid waste medium, LPDE films were buried for 100 days in a 1-L flask containing 400 g sterile solid waste raw materials at 28 degrees C. Each fungus was added to a separate flask. The moisture content and pH of the media were maintained at the optimal levels for each fungus. Photo-oxidation (25 days under UV-irradiation) was used as a pretreatment of the LDPE samples. The progress of the process was monitored by measurement of total organic carbon (TOC), pH, temperature and moisture. The results obtained from monitoring the process using isolated fungi under sterile conditions indicate that these fungi are able to grow in solid waste medium. The results of FT-IR and SEM analyses show that A. terreus and A. fumigatus, despite the availability of other organic carbon of materials, could utilize LDPE as carbon source. While there has been much research in the field of LDPE biodegradation under solid conditions, this is the first report of degradation of LDPE by A. fumigatus.