- Cellular membrane engineering for protein secretion in recombinant protein production
- Metabolic engineering for oligosaccharides and polysaccharides synthesis
- Biofuel and biorefinery
Dr. Chen's research, broadly defined as Biomolecular Engineering, interfaces Chemistry, Biology, and Chemical Engineering. By applying cellular membrane engineering, metabolic engineering, and other molecular engineering tools, her research addresses several fundamental issues associated with the Enzyme and Microbial Technology in biotechnological applications, especially in areas that impact medicine and the environment.
Cellular membrane engineering for protein secretion in recombinant protein production
E. coli is often the first choice as host microorganism for recombinant protein production, owing to its fast growth, simple nutrient requirement, well-studied physiology and a large number of expression systems. Extracellular secretion of recombinant proteins is highly desirable as it affords simple detection and purification, and a better folding environment free of cell-associated proteolytic degradation. Extracellular production system is particularly suitable for expression of proteins that are toxic to host cells. E. coli, however, is generally believed to be a poor secretor. Inadequate secretion is considered one of the most significant barriers of using E. coli as host for recombinant protein production. Through membrane engineering, the Chen group has developed an effective and generally applicable method for secretion of recombinant proteins. A single lpp gene deletion was demonstrated to significantly increase in the outer membrane permeability that allow high-percentage secretion of recombinant proteins to extracellular medium without cell lysis.
Metabolic engineering for oligosaccharides and polysaccharides synthesis
Oligosaccharides are important biomolecules which participate in various cellular processes. Oligosaccharides are key components of potential vaccines and treatments for diseases including cancer, HIV, malaria, and anthrax. However, these potential treatments are often limited by the cost and difficulty of synthesizing the oligosaccharide component. The Chen group has recently demonstrated that using an unconventional bacterium, Agrobacterium sp. ATCC 31749, oligosaccharides can be synthesized at concentrations as high as 20 mM without the use of expensive cofactors or nutrients. Building on the success with oligosaccharides, Dr. Chen's team has ventured into polysaccharide synthesis. Hyaluronan is a polysaccharide, important for several medical procedures such as ophthalmic surgery and arthritis treatment. Recombinant synthesis is of interest since the traditional extraction from rooster comb and fermentation with pathogenic strains raise safety concerns. Dr. Chen’s group has successfully engineered both E. coli and Agrobacterium sp strains for the synthesis of the polymer. This success not only provides a novel and safe method for producing the polymer but also offers an opportunity to further engineer/tailor the property of the polymer to enhance its performance in various biomedical applications.
Engineering for biofuel and biorefinery from renewable sources
Dr. Chen’s group has recently initiated an effort toward developing a new paradigm of biomass technology, which does not require complete hydrolysis of cellulose. The partial hydrolysis cellulose paradigm has several compelling advantages, which could be exploited to overcome critical barriers associated with the current paradigm. 1.) Reduced enzyme requirements and improved enzymatic hydrolysis; 2.) Enhanced process robustness: Microbial cells engineered to follow partial hydrolysis paradigm are more energetic and thus are better able to tolerate stresses from inhibitors and other unfavorable conditions. Compared to monosaccharide metabolism, intracellular metabolism of cellodextrin can utilize energy-saving mechanisms not available to glucose metabolism. For example, the Chen group has demonstrated the first example of engineering E. coli to assimilate cellobiose through a phosphorolysis. 3.) Increased productivity: Engineered cells to use cellodextrin directly could bypass natural regulatory mechanisms such as carbon catabolite repression that prevents microbial cells to simultaneously convert different types of biomass-derived sugars to biofuels.
- Energy and Sustainability