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Dr. Nancy Ho

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Background

The Saccharomyces yeast, also known as baker’s yeast, is the most effective microorganism for the fermentation of sugars to ethanol. This yeast has been the only microorganism used for the large-scale industrial production of ethanol, and has been used to make wine and bake bread since the dawn of civilization. The traditional feedstocks for ethanol production - cornstarch and cane sugar - contain polymers of glucose or simpler molecules made of glucose and fructose, which can all be effectively fermented by the Saccharomyces yeast to produce ethanol. Saccharomyces yeast has other characteristics as well that make it the most productive and desirable industrial microorganism for the production of ethanol. (See Why Yeast?)

In the 1970s, the world suffered its first energy crisis.  As a result, governments worldwide, particularly the US Government, strongly supported the development of alternative fuels for transportation, particularly a renewable liquid fuel that could be produced from domestically available renewable resources. Ethanol has been proven to be a desirable renewable liquid fuel for transportation. In particular, ethanol can be produced by not only fermenting sugars derived from food crops - such as cornstarch and cane sugar - but also from cellulosic biomass.  Cellulosic biomass (corn stover, rice straw, wood, grasses, waste papers, etc.) is the largest renewable resource in the world and is the most attractive feedstock for the production of ethanol fuel via microbial fermentation of its sugar molecules. 

The United States and many other parts of the world have tremendous amounts of cellulosic biomass, and more than 70% of this resource can be converted to sugars and fermented to ethanol by microorganisms, preferably Saccharomyces yeast.  However, the conversion of cellulosic biomass to ethanol requires the development of new technologies.  In particular, cellulosic biomass contains polymers comprised of two major sugars - glucose and xylose.

Unfortunately, the natural Saccharomyces yeast is unable to ferment xylose to ethanol. In the 1970s, research efforts were thus carried out worldwide to search for new microorganisms that could ferment both glucose and xylose to ethanol.  However, no such natural microorganisms were discovered. Therefore, in the early 1980s, a concerted effort was made by scientists in various countries, particularly in the United States, Europe, and Japan, to use recombinant DNA techniques to modify the Saccharomyces yeast to ferment xylose to ethanol. In the beginning, there were nearly ten groups worldwide focused on developing such recombinant yeast with at least half of the groups in the US. One such group was the Molecular Genetics Group at Purdue University (West Lafayette, Indiana) led by Dr. Nancy Ho. Not only was her group the smallest, but she also had to obtain her own funding to support this project.

This task turned out to be far more difficult than initially anticipated. One by one, the research groups fell by the wayside. Most experts concluded that it might not be possible to engineer the Saccharomyces yeast to ferment xylose.  By the end of the 1980s, there were only four groups worldwide that continued in this endeavor. Dr. Ho’s group was the only US group that persevered.  According to her analysis and design, she was certain that this task could be accomplished. She was also passionate that renewable cellulosic biomass be utilized, and thus, persisted with great determination. Compounding this task was the fact that after the oil crisis eased in the mid-1980s, it became far more difficult to obtain funding (in the US) for research to develop alternative fuels. On several occasions, she nearly had to terminate this project for lack of funding.

In the long run, her persistence paid off.  In 1993, Dr. Ho’s Purdue group succeeded in the development of the world’s first genetically engineered yeast that could effectively ferment xylose to ethanol.  In addition, her yeast, known as the Purdue Yeast, was also designed to effectively co-ferment a mixture of glucose and xylose together to ethanol, which is a crucial requirement for the efficient conversion of the major sugars present in cellulosic biomass.  This was accomplished by cloning three modified genes, XR, XD, and XK that are important for converting xylose to ethanol in the yeast.  The Purdue Group has continued to improve the Saccharomyces yeast with the goal of developing recombinant yeast ideally suited for large-scale industrial production of cellulosic ethanol.  In particular, they have made the yeast extraordinarily stable. This was accomplished by developing a new integration method so that all the cloned genes could be integrated into the yeast chromosomes in high-copy-numbers.

Academic institutes, government laboratories, and ethanol producers including ADM (Archer, Daniels, and Midland Company America – the world’s largest ethanol producer) have tested the Purdue yeast and validated its effectiveness in converting mixtures of glucose and xylose to ethanol from sugars in the crude hydrolysates of various types cellulosic biomass.  In April 2004, Iogen, a Canadian company, began to use the Purdue yeast to produce ethanol from wheat straw in the world’s first production plant of its kind. In addition, Iogen has publicly acknowledged that Purdue's recombinant glucose- and xylose-fermenting yeast is the most effective microorganism available for the production of ethanol from cellulosic materials (Purdue News release and ASM News letter, Oct 04, 2004).

Dr. Ho has treasured the opportunity to make the Saccharomyces yeast co-ferment glucose and xylose. That has made it possible to use the safe, effective yeast to produce ethanol as well as many other useful “green” chemicals from the world’s largest renewable resource – cellulosic biomass.

 

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