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Science 8 December 2006:
Vol. 314. no. 5805, pp. 1565 - 1568
DOI: 10.1126/science.1131969
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Research Articles

Engineering Yeast Transcription Machinery for Improved Ethanol Tolerance and Production

Hal Alper,1,3 Joel Moxley,1 Elke Nevoigt,1,2 Gerald R. Fink,3 Gregory Stephanopoulos1*

Global transcription machinery engineering (gTME) is an approach for reprogramming gene transcription to elicit cellular phenotypes important for technological applications. Here we show the application of gTME to Saccharomyces cerevisiae for improved glucose/ethanol tolerance, a key trait for many biofuels programs. Mutagenesis of the transcription factor Spt15p and selection led to dominant mutations that conferred increased tolerance and more efficient glucose conversion to ethanol. The desired phenotype results from the combined effect of three separate mutations in the SPT15 gene [serine substituted for phenylalanine (Phe177Ser) and, similarly, Tyr195His, and Lys218Arg]. Thus, gTME can provide a route to complex phenotypes that are not readily accessible by traditional methods.

1 Department of Chemical Engineering, Massachusetts Institute of Technology, Room 56-469, Cambridge, MA 02139, USA.
2 Department of Microbiology and Genetics, Berlin University of Technology, Seestrasse 13, D-13353 Berlin, Germany.
3 Whitehead Institute for Biomedical Research, 9 Cambridge Center, Cambridge, MA 02142, USA.

* To whom correspondence should be addressed. E-mail: gregstep{at}mit.edu

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