ChEMS Seminar: Protein Engineering for New Biocatalysts and Advanced Biomaterials

McDonnell Douglas Engineering Auditorium
Douglas S. Clark

Department of Chemical and Biomolecular Engineering
University of California, Berkeley

Abstract: Protein engineering enables the modification of existing proteins or the creation of entirely new ones for novel and improved functions. Accelerated rates of catalysis, enhanced stability against denaturants, higher binding affinities of ligands, and even programmed self-assembly and designed mechanical functions are currently possible and rapidly advancing with improved techniques and understanding of protein structure-function relationships. Application areas of protein engineering that we have recently focused on include the enzymatic synthesis of chiral molecules, and the development of advanced biomaterials. Examples of each will be discussed, and are introduced below.

Catalysis is central to modern chemistry, and transition metal catalysts are powerful tools for various transformations, not only in production of bulk chemicals, but also in fabrication of fine chemicals and biologically active compounds. Despite the immense progress in the field of chemical catalysis, the selectivity of such reactions for particular substrates of interest is often difficult to achieve with classic transition metal catalysts. In collaboration with Chemistry Professor John Hartwig and coworkers, we have transformed myoglobin and cytochromes P450 into novel enzymes that catalyze reactions that are not catalyzed by native Fe-enzymes. This approach enabled us to evolve a reconstituted artificial metalloenzyme containing an iridium porphyrin that exhibits kinetic parameters similar to those of natural enzymes. This strategy sets the stage to generate artificial enzymes from innumerable combinations of porphyrin-protein scaffolds and unnatural metal cofactors that catalyze a wide range of abiological transformations. 

Protein engineering also affords new opportunities to create protein building blocks that assemble into elaborate structures that serve as the basis for advanced biomaterials. For example, self-assembling protein templates have enormous potential for the fabrication of multifunctional nanostructures that require precise positioning of individual molecules, such as enzymes and inorganic moieties, in regular patterns. We are endeavoring to develop a standardized biomolecular construction kit composed of ultrastable filamentous proteins and connectors that assemble together into specific structures of controllable size and shape. Applications and materials currently under development include 2-D and 3-D patterning of metals and enzymes, biomolecular assemblies that perform mechanical functions and bioorganic hydrogels with tunable properties.

Bio: Douglas S. Clark is currently dean of the College of Chemistry and professor in the Department of Chemical and Biomolecular Engineering at the University of California, Berkeley. He is also the co-director of the Synthetic Biology Institute, faculty scientist at Lawrence Berkeley Laboratory, and holds the endowed G.N. Lewis Chair. Prior to his appointment as dean, Clark served as department chair of Chemical and Biomolecular Engineering and executive associate dean in the College of Chemistry. Clark has been a faculty member at Berkeley since 1986. He received his Ph.D. in chemical engineering from the California Institute of Technology in 1983 and a B.S. in chemistry, summa cum laude, from the University of Vermont in 1979. Clark is a leader in biochemical engineering, with particular emphasis on enzyme technology, biomaterials and bioenergy. Underlying these general topics is a longstanding interest in extremophiles and extremophilic enzymes. His work in biocatalyst engineering has created new opportunities for the application of enzymes in the pharmaceutical, chemical and agrochemical industries. Clark translated the use of combinatorial biocatalysis into commercial practice by co-founding the drug discovery company EnzyMed, Inc. His development of protein and cellular arrays has enabled high-throughput biosynthesis and activity/toxicity screening of potential drugs; this technology is also the basis of a startup company. He has published over 254 papers in peer-reviewed journals, has 28 patents and patent applications, and is the co-author of a textbook on biochemical engineering. Among his numerous honors and awards, Clark is a Fellow of the American Association for the Advancement of Science and the American Institute of Medical and Biomedical Engineers; he is the recipient of the James E. Bailey Award from the Society of Biological Engineering, the Marvin J. Johnson Award in Microbial and Biochemical Technology from the American Chemical Society, the Food, Pharmaceutical and Bioengineering Award of the American Institute of Chemical Engineers, the Amgen Award in Biochemical Engineering, the International Enzyme Engineering Award, and the NorCal Chemical Engineering Award—Industrial Research. He has also received the Departmental Chemical Engineering Teaching Award and the Presidential Young Investigator Award (National Science Foundation). Clark serves as editor in chief of Biotechnology and Bioengineering, and is on the editorial boards of Enzyme and Microbial Technology and Extremophiles.

Host: Allon Hochbaum