Yi Lu

Research

Our goals are to elucidate the role of metal ions in proteins and catalytic DNA/RNA, to design metalloenzymes with novel structures and functions, and to explore the use of the enzymes in biotechnological and pharmaceutical applications.

Metalloprotein design.

Metalloproteins catalyze difficult reactions with efficiency and selectivity that few other natural or artificial molecules can match. Little has been known about how to design a metalloprotein with desired structure and activity. We have been using stable, easy-to-produce, and well-characterized proteins as scaffolds for designing and engineering novel metalloproteins. Proteins of interest include heme-copper oxidase (a terminal oxidase of the respiratory chain), manganese peroxidase (a heme enzyme with great potential for providing renewable energy and destroying environmental pollutants), and cytochrome P450 (another heme enzyme involved in many regio-, stereo-, and enantio-selective chemical transformations).

Engineering artificial biocatalysts.

We are interested in making artificial biocatalysts by incorporating transition metal complexes into proteins. The combination of efficiency of the metal catalysts with the control and selectivity of proteins resulted in a new generation of asymmetric catalysts for synthesis of fine chemicals and chiral drug intermediates. Our syntheses are carried out under mild physiological conditions, using largely nontoxic reagents in aqueous solution. Since proteins are hydrophilic outside and hydrophobic inside, many transition metal catalysts that are not normally soluble in water can be made to be function in an aqueous environment. These features, together with the biodegradability of the products, make this an environmentally benign approach.

Catalytic DNA/RNA and biosensor.

Catalytic DNA/RNAs are a new class of metalloenzymes with great promise as pharmaceutical agents against AIDS and other retroviral diseases. We have developed new approaches for spectroscopic characterization of a catalytically active metal-binding site in catalytic DNA/RNAs, thus providing detailed structural and mechanistic information on thieir catalysis. We have also used an in vitro selection approach to obtain a group of new catalytic DNAs with both high metal-binding affinity for spectroscopy study and high reactivity for pharmaceutical applications. We aim to develop new DNA biosensors for simultaneous detection and quantification of bioavailable radionuclides and metal contaminants, such as lead, chromium, and mercury. The sensors will be highly sensitive and selective, not only for different metal ions, but also for different oxidation states of the same metal ion.

For more latest information about the Lu group research, please visit http://montypython.scs.uiuc.edu/.

Publications

"Fast Colorimetric Sensing of Adenosine and Cocaine Based on a General Sensor Design Involving Aptamers and Nanoparticles," Juewen Liu and Yi Lu, Angew. Chem. Int. Ed, 45, 90-94 (2006) [Full text] [News Link]

"Role of Heme Types in Heme-Copper Oxidases: Effects of Replacing a Heme b with a Heme o Mimic in an Engineered Heme-Copper Center in Myoglobin," N. Y. Wang, X. Zhao, and Y. Lu, J. Amer. Chem. Soc., 127, 16541-16547 (2005). [Full Text]

"Blue Ferrocenium Azurin: An Organometalloprotein with Tunable Redox Properties," H. J. Hwang, J. R. Carey, E. T. Brower, A. J. Gengenbach, J. A. Abramite, and Y. Lu, J. Amer. Chem. Soc., 127, 15356-15357 (2005). [Full Text]

"Stimuli-Responsive Disassembly of Nanoparticle Aggregates for Light-Up Colorimetric Sensing," J. Liu and Y. Lu, J. Amer. Chem. Soc., 127, 12677-12683 (2005). [Full Text]

"Proofreading and Error Removal in a Nanomaterial Assembly," J. W. Liu, D. P. Wernette, and Y. Lu, Angew. Chem. Int. Ed., 44, 7290-7293 (2005). [Full Text] [News Link] [Lu Lab Lab News]

"Axial Mehtionine Has Much Less Influence on Reduction Potentials in a CuA Center than in a Blue Copper Center," H. J. Hwang, S. M. Berry, M. J. Nilges and Y. Lu, J. Am. Chem. Soc., 127, 7274-7275 (2005) [Full Text]

"Design and Engineering of Metalloproteins Containing Unnatural Amino Acids or Non-native Metal-containing Cofactors," Yi Lu, Curr. Opin. Chem. Biol, 9, 118-126 (2005). [Full Text]

"Redox-Dependent Structural Changes in and Engineered Heme-Copper Center in Myoglobin: Insights into Chloride Binding to Cu_B in Heme Copper Oxidases," Xuan Zhao, Mark J. Nilges and Yi Lu, Biochemsitry 44, 6559-6564 (2005). [Full Text]

Awards

• Fellow, American Association for the Advancement of Science, 2007
• Society of Biological Inorganic Chemistry (SBIC) Early Career Award, 2007
• Howard Hughes Medical Institute Professors Award, 2002
• University Scholar Award (UIUC), 2002
• Award Runner-up for the Biosensors and Bioelectronics Award, 2002
• University of Illinois SCS Excellence in Teaching Award, 2000
• Camille Dreyfus Teacher-Scholar Award, 1999
• National Science Foundation Special Creativity Award
• Alfred P. Sloan Research Fellowship, 1998
• Cottrell Scholars Award (Research Corporation), 1997
• Beckman Young Investigator Award, 1996

Highlights

"Smart Nanomaterials Inspired by Biology: Dynamic Assembly of Error-Free Nanomaterials in Response to Multiple Chemical and Biological Stimuli", published in Accounts of Chemical Research was featured on the ACS Publications website as one of the Most-Cited Articles published in 2007 and cited through the period ending December 31, 2007

Dr. Lu's paper on Chemical Education was published in one of the most impacted magzine of general science, Science, and highlighted by Chemical and Engineering Newsw published by ACS.

For more highlights from the Lu group, go to http://montypython.scs.uiuc.edu/News/News.html.