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Felix Lam

Engineering tolerance in yeast for improved ethanol production

Baker’s yeast Saccharomyces cerevisiae is the organism of choice for the conversion of plant sugar (from corn or sugarcane, currently) to ethanol biofuel. At present, cellular toxicity to substrates or products in the fermentation medium remains one of the primary limitations of higher ethanol production. For example, ethanol itself becomes poisonous to yeast at concentrations greater than 15-20% (v/v) and hydrolysates of cellulosic biomass (widely considered as the next generation feedstock for renewable fuels) contain numerous deleterious compounds including aromatics, furfural, and acetic acid. To address the challenge of engineering enhanced tolerance, we are continuing our efforts to apply global transcriptional machinery engineering (gTME) in yeast. Briefly, gTME is a mutagenesis and selection technique where we perturb the expression profiles of hundreds of genes simultaneously by the introduction of a mutagenized basal transcription factor alongside the native, chromosomal allele. Selection under conditions of persistent, elevated stress (e.g., high ethanol + high glucose) yields strains whose superior phenotypes are synthesized from the combinatorial interplay of numerous up-regulated homeostasis mechanisms. Our current project aims to uncover phenotypes that maintain high ethanol productivity while exhibiting enhanced tolerance to combinations of stresses (including high ethanol, low pH, and/or high temperature).

 

Education

  • Ph.D.  (2006)  Biophysics, University of California, San Francisco.
  • S.B.  (1998)  Mechanical engineering, Massachusetts Institute of Technology.
  • S.B.  (1998)  Biology, Massachusetts Institute of Technology.

 

Publications

  • Lam, F.H., Hartner, F.S., Fink, G.R., Stephanopoulos, G. (2010) Enhancing stress resistance and production phenotypes through transcriptome engineering. Methods in Enzymology: Guide to Yeast Genetics, 2nd Edition. 470, 509-532.
  • Lam, F.H., Steger, D.J., O’Shea, E.K. (2008) Chromatin decouples promoter threshold from dynamic range. Nature. 453, 246-250.
  • Badarinarayana, V., Estep, P.W., Shendure, J., Edwards, J., Tavazoie, S., Lam, F., Church, G.M. (2001) Selection analyses of insertional mutants using subgenic-resolution arrays. Nature Biotech. 19, 1060-1065.