1. Da Silva Lab Molecular Biotechnology ndasilva@uci.edu ndasilva@uci.edu http://www.eng.uci.edu/users/nancy-da-silva Da Silva Lab Molecular Biotechnology ndasilva@uci.edu ndasilva@uci.edu http://www.eng.uci.edu/users/nancy-da-silva Research Summary: A major focus of our research is metabolic pathway engineering in yeast, focusing on both the development of improved methods and their application to diverse pathways. The research emphasizes molecular level design combined with subsequent application and analysis. Our work ranges from engineering Saccharomyces cerevisiae for the synthesis of polyketides (a very valuable class of pharmaceuticals) and collagen-based biopolymers, to engineering yeast for biorenewable and environmental applications. Current projects in my lab include: 1. Development of Tools for Metabolic Pathway Engineering Focus is on the stable introduction and expression of multiple genes to optimize pathway engineering in yeast 2. Microbial Metabolic Engineering for the Synthesis of Biorenewable Chemicals (Member of CBiRC, an NSF Engineering Research Center) 3. Metabolic Engineering of Yeast for Biofuels Production Use of cellulosomes to control the display of enzymes on the cell surface for increased synergy and rapid uptake of the released sugars 4. Optimizing S. cerevisiae for the Synthesis of Polyketides Primary focus are the fungal iterative polyketide synthases for 6-MSA and lovastatin synthesis 5. Synthesis and Characterization of Cell-Responsive Biopolymers Expression and application of collagen-based biopolymers useful for tissue engineering, drug delivery, and stem cell research Research Summary: A major focus of our research is metabolic pathway engineering in yeast, focusing on both the development of improved methods and their application to diverse pathways. The research emphasizes molecular level design combined with subsequent application and analysis. Our work ranges from engineering Saccharomyces cerevisiae for the synthesis of polyketides (a very valuable class of pharmaceuticals) and collagen-based biopolymers, to engineering yeast for biorenewable and environmental applications. Current projects in my lab include: 1. Development of Tools for Metabolic Pathway Engineering Focus is on the stable introduction and expression of multiple genes to optimize pathway engineering in yeast 2. Microbial Metabolic Engineering for the Synthesis of Biorenewable Chemicals (Member of CBiRC, an NSF Engineering Research Center) 3. Metabolic Engineering of Yeast for Biofuels Production Use of cellulosomes to control the display of enzymes on the cell surface for increased synergy and rapid uptake of the released sugars 4. Optimizing S. cerevisiae for the Synthesis of Polyketides Primary focus are the fungal iterative polyketide synthases for 6-MSA and lovastatin synthesis 5. Synthesis and Characterization of Cell-Responsive Biopolymers Expression and application of collagen-based biopolymers useful for tissue engineering, drug delivery, and stem cell research Prof. Nancy A. Da Silva Full Professor B.S. Chemical Engineering, U. Massachusetts, Amherst (1982) M.S. Chemical Engineering, California Institute. of Technology (1985) Prof. Nancy A. Da Silva Full Professor B.S. Chemical Engineering, U. Massachusetts, Amherst (1982) M.S. Chemical Engineering, California Institute. of Technology (1985) Key Publications: S. Srikrishnan, A. Randall, P. Baldi, N.A. Da Silva*. 2012. Rationally selected single-site mutants of the Thermoascus aurantiacus endoglucanase increase hydrolytic activity on cellulosic substrates. Biotechnol. Bioeng. In press. N.A. Da Silva*, S. Srikrishnan. 2012. MiniReview: Introduction and expression of genes for metabolic engineering applications in Saccharomyces cerevisiae. FEMS Yeast Res. In press. F. Fang, K. Salmon, M.W.Y. Shen, K.A. Aeling, E. Ito, B. Irwin, U. Tran, G.W. Hatfield, N.A. Da Silva*, S. Sandmeyer*. 2011. A vector set for systematic metabolic engineering in Saccharomyces cerevisiae. Yeast. 28:123-136. D. Shah, M.W.Y. Shen, W. Chen, N.A. Da Silva*. 2010. Enhanced arsenic accumulation in Saccharomyces cerevisiae overexpressing transporters Fps1p or Hxt7p. J. Biotechnol. 150:101-107. S.W.P. Chan, S.-P. Hung, S.K. Raman, G.W. Hatfield, R.H. Lathrop, N.A. Da Silva*, S.-W. Wang*. 2010. Recombinant human collagen and biomimetic variants using a de novo gene optimized for modular assembly. Biomacromolecules. 11:1460-1469. S.M. Ma, J.W.-H. Li, J. W. Choi, H. Zhou, K.K.M. Lee, V.A. Moorthie, X. Xie, J.T. Kealey, N.A. Da Silva, J.C. Vederas*, and Y. Tang*. 2009. Complete reconstitution of a highly-reducing iterative polyketide synthase. Science. 326:589-592. Key Publications: S. Srikrishnan, A. Randall, P. Baldi, N.A. Da Silva*. 2012. Rationally selected single-site mutants of the Thermoascus aurantiacus endoglucanase increase hydrolytic activity on cellulosic substrates. Biotechnol. Bioeng. In press. N.A. Da Silva*, S. Srikrishnan. 2012. MiniReview: Introduction and expression of genes for metabolic engineering applications in Saccharomyces cerevisiae. FEMS Yeast Res. In press. F. Fang, K. Salmon, M.W.Y. Shen, K.A. Aeling, E. Ito, B. Irwin, U. Tran, G.W. Hatfield, N.A. Da Silva*, S. Sandmeyer*. 2011. A vector set for systematic metabolic engineering in Saccharomyces cerevisiae. Yeast. 28:123-136. D. Shah, M.W.Y. Shen, W. Chen, N.A. Da Silva*. 2010. Enhanced arsenic accumulation in Saccharomyces cerevisiae overexpressing transporters Fps1p or Hxt7p. J. Biotechnol. 150:101-107. S.W.P. Chan, S.-P. Hung, S.K. Raman, G.W. Hatfield, R.H. Lathrop, N.A. Da Silva*, S.-W. Wang*. 2010. Recombinant human collagen and biomimetic variants using a de novo gene optimized for modular assembly. Biomacromolecules. 11:1460-1469. S.M. Ma, J.W.-H. Li, J. W. Choi, H. Zhou, K.K.M. Lee, V.A. Moorthie, X. Xie, J.T. Kealey, N.A. Da Silva, J.C. Vederas*, and Y. Tang*. 2009. Complete reconstitution of a highly-reducing iterative polyketide synthase. Science. 326:589-592.