- Protein and Enzyme Engineering
Proteins and enzymes are in the center of life processes. They form basic cellular structures and drive essential physiological reactions. This research thrust of our lab focuses on two aspects. First, harnessing the biocatalytic powers has led to the application of enzymes to various facets of science and technology. Stereospecificity and regioselectivity of enzyme catalysis attract the attentions of synthetic chemists. Mild reaction conditions and the ability to break complex natural molecules make enzymes indispensable for feedstock processing in biofuel industry. Applications of enzyme catalysis, regardless in vitro or in vivo, greatly benefit from a large selection of enzymes with diverse chemistry, desirable substrate specificity, fast kinetics, and exceptional stability. Our lab’s focuses on this aspect are the discovery, characterization, and engineering of enzymes for applications in bio-based chemical synthesis. Second, many proteins are also the substrates of enzymatic reactions. They are subjected to modifications, which often play critical roles for the function and correct folding. Our focus on this aspect is to build genetic encoding systems that will allow us to evade the natural regulatory mechanism and to directly install the desirable modifications. In addition to serving as useful tools in biochemical/biomedical studies, such system is also useful for the production of therapeutic proteins.
- Enzymes as Biocatalysts
Carboxyic Acid Reductases (CARs) are multidomain enzymes that catalyze the direct reduction of organic acids into corresponding aldehydes. Our lab works on the characterization and engineering of CARs for their diverse applications in biocatalysis for the syntheses of aldehydes as either the final products or as intermediates for subsequent formation of alcohols, amines, or hydrocarbons. (PDB ID: 5 MSD). CBET 1805528, CBET 2023250
- Genetic Encoding of Noncanonical Amino Acids
New functionality and chemistry can be introduced into proteins through the genetic encoding of noncanonical amino acids in live cells. Our lab engineers aminoacyl-tRNA synthetase to enable the incorporation of desirable functional groups into proteins of biomedical and pharmaceutical interests. (PDB ID: 1VBM) 1R01 GM138623, P20 GM113126
- Biopathway Design and Metabolic Engineering of Microbial Cell Factories
Nature is the true master of multistep synthesis. The beautiful and complex structures of various families of natural products are assembled from common intracellular metabolites following biosynthetic pathways that consist of numerous steps of enzyme-catalyzed reactions. However, the chemical needs for the survival of living organisms do not align perfectly with the chemical needs of human society. Many industrial chemicals that are essential to our everyday life are man-made, which means no natural producer has been identified, yet. Furthermore, naturally existing biosynthetic pathways may be recalcitrant to engineering. This research thrust focuses on designing and building new biosynthetic pathways to enable the efficient production of industrially important chemicals.
We devise artificial biosynthetic pathways to enable the microbial production of chemicals from renewable feedstocks, such as lignocellulosic materials. The metabolism of the microbial hosts are rewired in order to achieve optimal biosynthesis. CBET-1438332
- Cell Organelle Engineering
The bold vision of synthetic biology seeks precision controls of biological entities for the execution of pre-defined tasks. Such biological entity can be a microbiome/cell community, a single microbial species/cell line, a cellular organelle/virus, or macromolecules. In comparison to the other categories, cellular organelle/virus holds a unique position in bioengineering. Their complex chemical, physical, and sometimes genetic compositions enable high-level information processing for sophisticated tasks. Furthermore, their lack of self-propagation positions them as perfect tools for interfacing with host cells. This research thrust is highly fundamental and exploratory.
Carboxysomes are proteinaceous compartments that encapsulate essential enzymes for CO2 fixation. Our lab studies molecular details in the assembly of a-type carboxysome for its engineering as nano-scale biochemical reactors.
