MIT Engineered Yeast Improves Ethanol Production

7 December 2006

MIT scientists have engineered yeast that can improve the speed and efficiency of ethanol production. By manipulating the yeast genome, the researchers have engineered a new strain of yeast that can tolerate elevated levels of both ethanol and glucose, while producing ethanol faster than un-engineered yeast. The work is reported in the Dec. 8 issue of Science.

The MIT strategy is to manipulate the genes encoding proteins responsible for regulating gene transcription and, in turn, controlling the repertoire of genes expressed in a particular cell. These types of transcription factors bind to DNA and turn genes on or off, essentially controlling what traits a cell expresses.

The traditional way to genetically alter a trait, or phenotype, of an organism is to alter the expression of genes that affect the phenotype. But for traits influenced by many genes, it is difficult to change the phenotype by altering each of those genes, one at a time.

Targeting the transcription factors instead can be a more efficient way to produce desirable traits.

It is the makeup of the transcripts that determines how a cell is going to behave and this is controlled by the transcription factors in the cell.

—Gregory Stephanopoulos,co-author

The MIT researchers are the first to use this new approach. In this case, the researchers targeted two different transcription factors. They got their best results with a factor known as a TATA-binding protein, which when altered in three specific locations caused the over-expression of at least a dozen genes, all of which were found to be necessary to elicit an improved ethanol tolerance, thus allowing that strain of yeast to survive high ethanol concentrations.

Because so many genes are involved, engineering high ethanol tolerance by the traditional method of overexpressing individual genes would have been impossible, according to Hal Alper, a postdoctoral associate in the laboratories of Professor Gregory Stephanopoulos. Furthermore, the identification of the complete set of such genes would have been a very difficult task, Stephanopoulos adds.

The high-ethanol-tolerance yeast also proved to be more rapid fermenters: The new strain produced 50% more ethanol during a 21-hour period than normal yeast.

The prospect of using this approach to engineer similar tolerance traits in industrial yeast could dramatically impact industrial ethanol production, a multi-step process in which yeast plays a crucial role. First, cornstarch or another polymer of glucose is broken down into single sugar (glucose) molecules by enzymes, then yeast ferments the glucose into ethanol and carbon dioxide.

The research was funded by the DuPont-MIT Alliance, the Singapore-MIT Alliance, the National Institutes of Health and the US Department of Energy.

Resources:

• “Engineering Yeast Transcription Machinery for Improved Ethanol Tolerance and Production”; Hal Alper, Joel Moxley, Elke Nevoigt, Gerald R. Fink, Gregory Stephanopoulos; Science 8 December 2006:Vol. 314. no. 5805, pp. 1565 - 1568 DOI: 10.1126/science.1131969