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Expanding the potential of metabolic engineering

BY Emily Scott

For decades, scientists have used the natural processes in cells to create useful products such as chemicals and biofuels. 

This process, known as metabolic engineering, modifies the gene networks within cells to increase an organism’s ability to produce a specific substance. 

Professor Huimin Zhao, Steven L. Miller Chair of Chemical and Biomolecular Engineering
Professor Huimin Zhao, Steven L. Miller Chair of Chemical and Biomolecular Engineering, leads the IGB's Biosystems Design research theme.

But this field has been limited because only a few organisms are used to create products, both in metabolic engineering research and in industry. Over the last 50 years, the most common production hosts are two “model organisms,” Saccharomyces cerevisiae and E. coli

However, several other “non-model organisms” exist, and they have capabilities that these “model organisms” lack. 

A new research endeavor, led by Professor Huimin Zhao, Steven L. Miller Chair of Chemical and Biomolecular Engineering, aims to gain a better understanding of two non-model organisms with unique characteristics that could help create specific products. 

Understanding what these non-model organisms have to offer means that, in the future, there will be more choices for production hosts — and thus, a greater variety of products that can be made. 

Zhao and a group of co-investigators are exploring what these organisms can provide in a project funded by a five-year, $8.3 million grant from the U.S. Department of Energy through its Biosystems Design initiative.

This team of co-investigators includes Christopher Rao, professor of chemical and biomolecular engineering at Illinois, Professor Joshua Rabinowitz and Martin Wühr from Princeton University, Professor Costas Maranas from Pennsylvania State University, and Dr. Yasuo Yoshikuni from the Joint Genome Institute.  

“We want to understand what makes these organisms so special,” said Zhao, who is the leader of the Biosystems Design (BSD) theme at the IGB. 

The two organisms —Rhodosporidium toruloides and Issatchenkia orientalis — are both species of yeast with useful properties. 

R. toruloides can produce lots of lipids, which are molecules that store energy and build up cell membranes. More lipids means it can produce large amounts of fatty acids and fatty alcohols — which are derived from lipids. 

I. orientalis can survive at a low pH level — something S. cerevisiae cannot do. The ability to function in acidic environments will help produce organic acids. 

To test manipulations on these non-model organisms, Zhao hopes to use a variety of experimental strategies, including a new, more efficient method he recently developed with other researchers in the BSD theme. 

They also hope to develop tools that would target and test every gene in the organism’s genome at once, revealing which genetic manipulations will be useful for the production of chemicals and fuels in a more efficient manner. 

These tools can be combined with computational models, which are often used in metabolic engineering; they map the cellular networks that scientists need to understand and modify. 

Zhao said combining experimental approaches with computational ones would speed up the process. 

Overall, they hope to gain a better understanding of these non-model organisms, which could be the key to more efficient metabolic engineering. 

“We’re more interested in just the knowledge about these organisms,” Zhao said. “And also, the tools that we want to develop so that we can readily engineer them for the production of valuable chemicals and fuels.” 

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