Ka-Yiu San

Research Interests:

• Genomic and metabolic engineering; biochemical engineering; biotechnology

Education:

• B.S. (1978) Rice University
• M.S. (1981) California Institute of Technology
• Ph.D. (1984) California lnstitute of Technology

Our laboratory is mainly concerned with the development of new concepts and novel appoaches of designing and manipulating metabolic routes using recombinant DNA technology to improve cellular activities and to achieve more advanced production systems. The main focus is on the development of a framework for the systematic analysis of the cellular responses in regulating its metabolic activities upon precise genetic perturbations. Understanding these responses is critical to design organisms and processes for efficient and reliable manufacturing of gene products from recombinant cells.

Metabolic Engineering - Cofactor manipulations in Escherichia coli: Most current metabolic engineering studies have focused on manipulations of enzyme levels and the effect of amplification, addition or deletion of a particular pathway. A newer focal area in our laboratory is the manipulation of cofactors, which play a major role in cell physiology and in the production of many important fermentation products. Additionally these cofactors are essential for a large class of enzymatic reactions. For example, the NADH/NAD+ pair serves as donor and/or acceptors of electrons in many biological redox reactions. The foucs of our current research is to investigate the effect of different cofactor manipulations using cofactor-dependent products as model systems.

Plant metabolic Engineering: In a joint project with Dr. Shanks of Iowa State University and Dr. Gibson, our lab explores the area of metabolic engineering in plants. We are particularly interested in the metabolic engineering of the indole pathway and its subsequent effect on indole alkaloid biosynthesis in Catharanthus roseus hairy roots. C. roseus produces a wide variety of indole alkaloids including the anti-cancer drugs vincristine and vinblastine. Hairy roots have a number of advantages over cell cultures including increased genetic stability and substantially higher alkaloid content.

Quantitative Systems Biotechnology: Recent rapid accumulation of enormous amount of genomic and pathway information provides a unique opportunity for the optimal design of genetic circuits and/or metabolic pathways to achieve a specific cellular behavior. Our laboratory is interested in the development of new analysis and design methodologies for the efficient utilization of these massive genomic and pathway knowledge.

Selected Publications

1. Berríos-Rivera, S. J., Bennett, G. N., and San, K.-Y. San, "Metabolic Engineering of Escherichia coli through Genetic Manipulation of NADH Availability", Metabolic Engineering, in press (2002).
2. Berríos-Rivera, S. J., Bennett, G. N., and San, K.-Y., "The Effect of Manipulating NADH Availability on the Redistribution of Metabolic Fluxes in Escherichia coli Chemostat Cultures", Metabolic Engineering, in press (2002).
3. Berríos-Rivera, S. J., San, K.-Y., and Bennett, G. N., "The Effect of Naprtase Overexpression on the Total Levels Of NAD, the NADH/NAD+ Ratio, and the Distribution of Metabolites in Escherichia coli", Metabolic Engineering, in press (2002).
   
4. Hughes, E. H., Hong, S.-B., Shanks, J. V., San, K.-Y., Gibson, S. I., "Characterization of an Inducible Promoter System in Catharanthus roseus Hairy Roots", Biotechnology Progress, accepted (2002).
5. Berríos-Rivera, S. J., San, K.-Y., and Bennett, G. N., "The Effect of Carbon Sources and Lactate Dehydrogenase Deletion on 1,2-Propanediol Production in Escherichia coli", Journal of Industrial Microbiology and Biotechnology, accepted (2002).
   
6. San, K.-Y., Bennett, G.N., Berríos-Rivera, S.J., Vadali, R.V., Yang, Y.-T., Horton, E., Rudolph, F.B., Berna Sariyar, B., Backwood, K., "Metabolic Engineering through Cofactor Manipulation and Its Effects on Metabolic Flux Redistribution in Escherichia coli", Metabolic Engineering, 4:182-192 (2002).
7. Wardwell, S.A., Yang, Y.-T., Chang H.-Y., San, K.-Y., Rudolph, F.B., Bennett, G.N., "Expression of the Klebsiella pneumoniae CG21 Acetoin Reductase Gene in Clostridium acetobutylicum ATCC 824", J Ind Microbiol Biotechnol, 27:220-7 (2001).
8. Yang, Y.-T, Bennett, G. N., and San, K.-Y., "The Effects of Feed and Intracellular Pyruvate Levels on the Metabolic Fluxes Redistribution in Escherichia coli with Fermentative Lactate Dehydrogenase Overexpression", Metabolic Engineering, 3:115-123 (2001).
9. Bennett, G.N. and San, K.-Y., "Microbial Formation, Biotechnological Production and Applications of 1,2-Propanediol", App. Micro. Biotech., 55:1-9 (2001).
10. Yang, Y.-T, Peredelchuk, M., Bennett, G. N., and San, K.-Y., "The Effect of Variation of Klebsiella pneumoniae Acetolactate Synthase Expression on Metabolic Fluxes Redistribution in Escherichia coli", Biotechnology and Bioengineering, 69:150-159 (2000).
11. Susana J. Berríos-Rivera, Yang, Y.-T., Bennett, G. N., San, K.-Y., "Effect of Glucose Analog Supplementation on Metabolic Flux Distribution in Anaerobic Chemostat Cultures of Escherichia coli" Metabolic Engineering, 2:149-154 (2000).
12. Yang, Y.-T, Bennett, G. N., and San, K.-Y., "The Interactions of Nuo and Ack/pta Mutations on Metabolic Flux Redistribution in Escherichia coli", Biotechnology and Bioengineering, 65:291-297 (1999).

CHEMICAL & BIOMOLECULAR ENGINEERING DEPT. MS-362
Rice University PO Box 1892 Houston, Texas 77251-1892	E-mail: chbe@rice.edu	Phone: (713) 348-4902 FAX:(713) 348-5478