Lianhong Sun
Lianhong Sun, Assistant Professor
221 Goessmann
413-545-6143 (office)
413-545-1647 (FAX)
lsun@ecs.umass.edu
Sun Research Group
Education
B. S. Chemistry, Inner Mongolia Univ., 1994
M. S., Physical Chemistry, Dalian Inst. of Chemical Physics, Chinese Academy of Sciences, 1997
Ph.D., Chemistry, California Institute of Technology, 2003
Current Focus of Research
Using biocatalysts or enzymes in a chemical process has been regarded as an efficient approach to improving productivity and reducing waste generation. An effective bioprocess generally comprises enzymes with desired reactivity and stability, however, a robust regulatory system is essential to strictly control enzymatic activities in a pathway to achieve maximal yields and conversion rates. We are interested in 1. engineering enzymes for industrially important biotransformation reactions, 2. assembling biochemical pathways to synthesize biologically significant small molecules, and 3. designing genetic circuits to control biological systems. We employ molecular biology methods, along with engineering principles, to create biomolecules and biological systems with a variety of applications in the pharmaceutical industry, biomedical engineering and material sciences. Our goal is to create useful biomolecules and biological systems, and to illuminate the fundamental design principles of biological complex systems.
Evolutionary Enzyme Design and Engineering
Enzymes are well-known as efficient and marvelous catalysts, but a significant portion of them notoriously function under industrial environment for their instability and limited catalytic diversity. To enhance the applicability of enzymes in chemical processes, functions and properties of the enzymes need to be tailored. An evolutionary algorithm, directed evolution, has been applied to enhance and create novel functions of enzymes. This method combines screen/selection with random mutation/recombination to fish out enzyme variants with improved properties from a library in each round of directed evolution experiments, and the identified mutants serve as starting materials for the next round of directed experiments. This iterative process eventually allows us to obtain enzymes with desired properties. Thermostability, specific activity, expression levels, substrate specificity and enatioselectivity all have been improved using directed evolution. We are using this technology, focusing on industrially important bioconversion reactions, to generate useful biocatalysts with desired functions.
Biochemical Engineering of Plant Secondary Metabolics
Plant secondary metabolites are important medicinally significant small molecule therapeutics. They have complex structures with multi optical centers, exhibiting diverse biological activities. Traditional organic synthesis of these metabolites are seriously hindered due to their complexity, especially for the chirality. We use molecular cloning methods to functionally express biosynthetic genes of plan secondary metabolites in microorganisms to establish alternative bioconversion pathways to synthesize them in vivo. By further manipulating gene expression and gene regulating pathways, metabolic fluxes can be directed for the optimal yield of desired molecules. These synthetic strategies can achieve efficient conversion of raw materials with limited waste generation under mild and well-controlled reaction conditions, representing energy efficient and environmentally benign green chemistry processes.
Synthetic Biology
Biological systems function as complex systems for their adaptability and emergence. However, the design principles for their robustness and functionality are far from unveiled, while these principles are essential to design predictable biological systems for biomedical applications. We are interested in designing conceptually simple yet representative biological systems with controllable, adjustable and predictable functions, so that the basic design guidelines can be illustrated to understand large scale biological systems. An important feature in our artificial biological systems is the interaction among subsystems, which is a basic phenomenon in complex biological systems. In addition to be used to understand larger scale biological systems, these biological systems are potential biological control systems, expected to be useful for biomedical engineering.
Selected Publications
Sun, L. and Yagasaki, M., Screen for oxidase by detection of hydrogen peroxide with horseradish peroxidase. In Methods of Molecular Biology, 230, 177-182, 2003. Directed Enzyme Evolution: Screening and Selection Methods (Arnold, F. H. and Georgiou, G. Eds.) Humanna Press Inc., Totowa, NJ.
Salazer, O. and Sun, L., Mutant library analysis. In Methods of Molecular Biology, 230, 85-98, 2003. Directed Enzyme Evolution: Screening and Selection Methods. (Arnold, F.H. and Georgiou, G. Eds.). Humanna Press Inc., Totowa, NJ.
Georgescu, R., Bandara, G. and Sun, L., Saturation mutagenesis. In Methods of Molecular Biology, 230, 75-84, 2003. Directed Evolution: Library Creation. (Arnold, F. H. and Georgiou, G. Eds.). Humanna Press Inc., Totowa, NJ.
Arnold, F. H., Sun, L. and Petrounia, I. P., Novel Glucose 6-Oxidase. USA Patent Serial No. 10/375,909.
Sun, L., Butler, T., Alcalde, M., Petrounia, I. P. and Arnold, F. H., Modification of galactose oxidase to introduce glucose 6-oxidase activity. ChemBioChem, 3, 781-783, 2002.
Sun, L., Petrounia, I. P., Yagasaki, M., Bandara, G. and Arnold, F. H., Expression and stabilization of galactose oxidase in Escherichia coli by directed evolution. Protein Engineering, 14, 699-704, 2001.
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