Metabolic engineering for inhibitor tolerance

Economically viable production of biorenewable fuels and chemicals is highly dependent on both the ability to achieve a high product titer and utilize high concentrations of cheap (“dirty”) fermentation substrates. Both of these process properties require that the microbial biocatalyst be able to tolerate certain inhibitory compounds. This problem was recently described in our October 2011 Current Opinion in Chemical Engineering review article.

One of the long-term goals of Dr. Laura Jarboe’s lab is to be able to rationally engineer biocatalyst tolerance with the same predictive, rational approach that is currently used to rationally engineer biocatalyst metabolism. This includes studies to identify the mechanism of inhibition and evolutionary studies coupled with reverse engineering. Dr. Jarboe currently has two projects in this area.

1.1 NSF Engineering Research Center for Biorenewable Chemicals (CBiRC ERC)
CBiRC aims to produce biorenewable drop-in industrial chemicals through a combination of biological catalysis and chemical catalysis. Some of the compounds that serve as a trade-off point between the biological process and the chemical process are inhibitory to the bacteria and thus could limit the ultimate process yield and productivity. Here she and her researchers focus on engineering of microbial biocatalysts for tolerance of these compounds. Two PhD candidates, Liam Royce (CBE) and Ping Liu (microbiology), are working on this project. This work is funded by the NSF.

1.2 Hybrid Processing
The production of biorenewable fuels and chemicals from lignocellulosic biomass (such as switch grass and corn stover) is very important for energy independence and production of affordable transportation fuels and commodity chemicals. However, the processing of this biomass into substrates that can be used by the bacteria remains a major challenge. Existing technologies include enzymatic digestion, acid/steam hydrolysis and the use of ionic liquids. Each of these methods has their own challenges. Here we have proposed that thermochemical processing (pyrolysis) could be an effective, economically viable method of biomass processing. ISU researchers have developed excellent thermochemical processing methods for producing “pyrolytic sugars” from biomass. The goal of our research team is to enable effective microbial utilization of these pyrolytic sugars, as well as other products of the pyrolysis process. This includes development of both improved microbes and pretreatment methods for the fermentation substrates. The Biorenewables Research Laboratory (BRL) dedicated to this work is described here. Our recent publications on this project include this 2011 review and this paper describing the metabolic engineering of ethanologenic E. coli for utilization of the pyrolytic sugar levoglucosan.

In May 2012 and May 2013 Dr. Jarboe hosted a “Hybrid Processing” workshop on this topic, with funding from the ISU PSI, ISU Office of Biotechnology and ISU Bioeconomy Institute. Meeting materials are available here

This work is a collaboration with Zhiyou Wen (FSHN), Robert Brown and Shendge Zhou at Northern Illinois University. Current Jarboe lab members working on this project are postdoctoral researcher/lab manager Zhanyou Chi and CBE PhD student Tao Jin. Funding for this project has been awarded by NSF Energy for Sustainability Program, Iowa Energy Center, ISU’s Plant Science Institute and ISU’s Bioeconomy Institute.

Laura Jarboe’s other chemical engineering project