Development of whole cell-biosensors for reducing byproduct formation in industrial fermentations and other applications

Large-scale bioreactors can be used for growth of bacterial cells, as well as other types of cells such as yeast or animal cells. In these bioreactors, control systems have been implemented to regulate key process conditions, such as temperature, pH, dissolved oxygen level, and nutrient concentration, near the optimal levels to maximize formation of desired products. However, it is difficult to achieve homogeneous conditions throughout the bioreactor vessel for very large bioreactors. Nutrients and gases must be introduced at specific locations in the bioreactor where connections are available and limitations in mixing can lead to variations in concentration throughout the bioreactor.

As an example, in E. coli fermentation, oxygen limitations due to poor mixing can lead to production of organic acid byproducts like acetate, which may reduce yield of desired products like recombinant proteins. When process changes are not sufficient to reduce heterogeneity leading to byproduct formation, changes to the cell may be necessary. We are interested in screening oxygen sensitive promoters in order to design cells that sense when they are becoming oxygen limited and reduce expression of enzymes that lead to byproduct formation.

Oxygen sensitive promoters can also be important in development of engineered probiotics. Engineered probiotics are microorganisms that can be integrated into the gut microbiome, sense environmental conditions there, and report on those conditions or produce a therapeutic.

Examples of student posters and talks on this work (*denotes mentored undergraduate):

  • C. M. Gray*, I.M.B. Reizman. Poster: Construction of a plasmid for use in whole-cell biosensors to detect oxygen levels. Indiana Academy of Science Annual Meeting, March 2022.
  • C. M. Meiser*, R.K. Klauer*, I.M.B Reizman. Poster: Development of an oxygen biosensor in Escherichia coli. Wabash Valley ACS Undergraduate Research Conference, October 2017.
  • A. Armstrong*, I.M.B. Reizman, E. Reyes. Oral presentation: Low-cost modification of a lab scale bioreactor to simulate oxygen gradient heterogeneities present in large-scale industrial bioreactors. Rose-Hulman Undergraduate Mathematics Conference, April 2017.




Production of value-added chemicals from renewable feedstocks

Distillers corn oil (DCO) is an important co-product that can be recovered during dry-grind ethanol production.  Ethanol plants can currently gain income from DCO by selling it for animal feed or converting it to biodiesel.  However, the fatty acids in DCO are potentially a valuable source of raw materials to produce specialty chemicals used in biopolymers, lubricants, and personal care products. Several student projects have focused on optimization of a bioconversion process for dicarboxylic acid production from DCO, as dicarboxylic acids are potentially a valuable feedstock for biopolymers. Additional investigations are focused on evaluation of bio-derived catalysts for biodiesel production from DCO.

Examples of student publications, posters, and talks on this work (*denotes mentored undergraduate):

  • T.S. Pirner*, N.A. Palmer*, I.M.B. Reizman. Techno-economic assessment of a bioprocess for long-chain dicarboxylic acid production from vegetable oils: A case study for distillers corn oil. Biomass Conversion and Biorefinery (2022).
  • S. Jin*, G.T. Neumann, I.M.B. Reizman. Poster: Production of Dicarboxylic Acids by Biotransformation of Oleic Acid using Candida viswanathii. AIChE Annual Meeting, November 2019.
  • X. Tang*, G.T. Neumann, I.M.B. Reizman. Oral presentation: Analysis of Carbohydrates, Dicarboxylic Acids, and Fatty Acids from Fermentation Broth by HPLC-DAD and HPLC-RID. Indiana Academy of Science Annual Meeting, March 2019.
  • J.A. Mobley, N.A. Palmer*, K.S. Ryan*, A.M. DeFries, I.M.B. Reizman. Poster: Investigation of the Production of Long Chain Dicarboxylic Acids from Distillers Corn Oil Using Candida viswanathii. Corn Utilization and Technology Conference, June 2018.


Image credits:

  1. Bioreactor (CC BY-NC-ND 2.0
  2. Biofuel (CC BY 2.0