CBI research is accelerating the process of engineering microbes to produce bioproducts.

Supercomputing meets modular design: Developing bioproducts faster and more affordably

Microbes can produce a large array of compounds from biomass sources, like grasses, woody plants  and crop wastes, by using their own enzymes to trigger chemical changes. However, bioengineering a microbe to create each new product can take many years and a significant investment.

Research funded by the Center for Bioenergy Innovation (CBI) is speeding up that process. In a large-scale benchmark study recently published in Metabolic Engineering, scientists demonstrated a technique called modular cell design. In this innovative approach, a bacterial cell functions much like a motor vehicle chassis that can be enhanced with various performance features.

“Modular design is all around us. It’s in our buildings, your furniture – even your burger,” said lead researcher Cong Trinh, an associate professor of chemical and biomolecular engineering at the University of Tennessee in Knoxville. “When you order your burger, you optimize it by adding your favorite toppings. Through evolution in nature, cells already utilize this kind of modular design. The question is: How does it work?”

Trinh and coauthor Sergio Garcia used high-performance computing at Oak Ridge National Laboratory to evaluate thousands of reactions within a cell, simulating which enzyme pathways would lead to different outcomes. Using this information, they created “production modules” containing enzymatic pathways that could be plugged into the chassis cell to produce desired compounds.

“Think of it like the U.S. highway system. Your highway is the chassis of the cell,” Trinh said. “Within the living cell, we need to build a map to our destination.”

Building on previous discoveries through CBI, Trinh and Garcia demonstrated that three modules in E. coli bacteria were relatively easy to direct this way. The scientists reprogrammed the cells repeatedly to enhance their production of 161 different natural compounds. In the process, they also modified the cell metabolism to eliminate the creation of unwanted byproducts. This represented a huge leap from the typical speed of bioengineering for specific products one at a time.

Trinh said the same method can eventually be part of a “plug and play” approach to bioengineering other bacteria cells to produce commercial products, materially reducing research and development costs.

“This is really significant if you want to make molecules from renewable feedstocks,” Trinh said. “It lets you do the same thing with a biological system that you’ve done with petroleum for years, but in a more renewable and sustainable way.”

CBI at Oak Ridge National Laboratory is one of four Department of Energy Bioenergy Research Centers focused on advancing biofuels and bioproducts for a vibrant domestic bioeconomy. CBI is accelerating the development of bioenergy-relevant plants and microbes to enable production of drop-in sustainable aviation fuel, bioproducts that sequester carbon, and sustainable replacements for plastics and other environmentally harmful products.

This research used resources at the Oak Ridge Leadership Computing Facility, a DOE Office of Science user facility at ORNL.