Isobutanol production freed from biological limits using synthetic biochemistry

Saken Sherkhanov, Tyler P. Korman, Sum Chan, Salem Faham, Hongjiang Liu, Michael R. Sawaya, Wan-Ting Hsu, Ellee Vikram, Tiffany Cheng and James U. Bowie ()
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Saken Sherkhanov: Molecular Biology Institute, UCLA-DOE Institute, University of California
Tyler P. Korman: Molecular Biology Institute, UCLA-DOE Institute, University of California
Sum Chan: Molecular Biology Institute, UCLA-DOE Institute, University of California
Salem Faham: Vertex Pharmaceuticals
Hongjiang Liu: Molecular Biology Institute, UCLA-DOE Institute, University of California
Michael R. Sawaya: Molecular Biology Institute, UCLA-DOE Institute, University of California
Wan-Ting Hsu: Molecular Biology Institute, UCLA-DOE Institute, University of California
Ellee Vikram: Molecular Biology Institute, UCLA-DOE Institute, University of California
Tiffany Cheng: Molecular Biology Institute, UCLA-DOE Institute, University of California
James U. Bowie: Molecular Biology Institute, UCLA-DOE Institute, University of California

Nature Communications, 2020, vol. 11, issue 1, 1-10

Abstract: Abstract Cost competitive conversion of biomass-derived sugars into biofuel will require high yields, high volumetric productivities and high titers. Suitable production parameters are hard to achieve in cell-based systems because of the need to maintain life processes. As a result, next-generation biofuel production in engineered microbes has yet to match the stringent cost targets set by petroleum fuels. Removing the constraints imposed by having to maintain cell viability might facilitate improved production metrics. Here, we report a cell-free system in a bioreactor with continuous product removal that produces isobutanol from glucose at a maximum productivity of 4 g L−1 h−1, a titer of 275 g L−1 and 95% yield over the course of nearly 5 days. These production metrics exceed even the highly developed ethanol fermentation process. Our results suggest that moving beyond cells has the potential to expand what is possible for bio-based chemical production.

Date: 2020
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DOI: 10.1038/s41467-020-18124-1

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