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Creating alternative petrochemical processes with yeast

Scientists are attempting to find more efficient and cleaner ways to power the world as climate change continues to wreak havoc on our planet. Biological systems could be an enticing alternative to common petrochemical processes that produce considerable greenhouse emissions and other waste items.

Michael Jewett of Northwestern Engineering and academics from the University of Texas at Austin have recently collaborated to improve our understanding of biochemical processes and boost the rate at which biological systems produce chemicals. The discoveries could help us get closer to establishing long-term alternatives to oil-based materials, fuels, and other items.

The paper "An Integrated In Vivo/In Vitro Framework to Enhance Cell-Free Biosynthesis with Metabolically Rewired Yeast Extracts," published in Nature Communications on Aug. 26, describes the development of optimized in vitro biosynthesis (biochemical production) processes that use cell extracts from engineered Saccharomyces cerevisiae (brewer's yeast). Blake Rasor, a PhD student in Jewett's lab, co-authored the work alongside Jewett, the Walter P. Murphy Professor of Chemical and Biological Engineering at the McCormick School of Engineering. The examination was carried out in partnership with Hal Alper's research group at the University of Texas.

The work was funded by the Emerging Technologies Opportunity Program of the US Department of Energy Joint Genome Institute (ETOP). The ETOP provides money to help researchers throughout the world create innovative technologies by utilizing JGI's user programs to promote energy and environmental applications.

S. cerevisiae is a highly controlled framework for biochemical production, thanks to decades of metabolic studies and genetic tool development. This yeast has been designed to create numerous target compounds utilized in industrial and therapeutic purposes, in addition to its traditional uses in baking and brewing.

Cellular production systems, on the other hand, are torn between producing more cells and producing the engineered output. Breaking the biological machinery out of cells and using the extracted material for cell-free biochemical reactions allows Jewett's group to circumvent these growth and survival limits, allowing for the optimization of levers that are difficult to tune in living cells.

Previously, unaltered E. coli strains were employed in cell-free biosynthetic experiments with crude cell extracts. The researchers broadened the breadth of this method by adding S. cerevisiae extracts and cellular metabolic engineering approaches to boost the biosynthetic potential of cell-free processes. This shows that metabolic rewiring in cells results in extracts and cell cultures with higher volumetric outputs than wildtype (unchanged) extracts and cell cultures.

The ability to produce three chemical products (butanediol, glycerol, and itaconic acid) at a rate up to ten times quicker than cellular techniques demonstrates the versatility and usefulness of combining cellular engineering and cell-free biosynthesis.

"This could broaden the range of biological systems powering sustainability efforts," says the researcher.

"Our study contributes to an emerging field of science that tries to create cellular function, on-demand biomanufacturing, and portable diagnostics using cell-free systems derived from crude cell extracts," said Jewett, head of the Center for Synthetic Biology. "These efforts, in effect, are broadening the scope of biomanufacturing in order to create a sustainable bioeconomy."

Next steps, according to Jewett and his coworkers, include route prototyping in the setting of changing metabolism, as well as cell-free biomanufacturing to supplement current cell-based techniques.

"Improving the scale of cell-free reactions and expanding the integrated cell/cell-free metabolic engineering strategy to yeast strains producing other value-added biochemical products could spearhead the development of sustainable, economically viable alternatives to current chemical production processes," he said.

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