Abstract
Organic acids are valuable platform chemicals for future biorefining applications. Such applications involve the conversion of low-cost renewable resources to platform sugars, which are then converted to platform chemicals by fermentation and further derivatized to large-volume chemicals through conventional catalytic routes. Organic acids are toxic to many of the microorganisms, such as Escherichia coli, proposed to serve as biorefining platform hosts at concentrations well below what is required for economical production. The toxicity is two-fold including not only pH based growth inhibition but also anion-specific effects on metabolism that also affect growth. E. coli maintain viability at very low pH through several different tolerance mechanisms including but not limited to the use of decarboxylation reactions that consume protons, ion transporters that remove protons, increased expression of known stress genes, and changing membrane composition. The focus of this mini-review is on organic acid toxicity and associated tolerance mechanisms as well as several examples of successful organic acid production processes for E. coli.
Highlights
CFiognucreept1ual model of toxicity in biorefining applications Conceptual model of toxicity in biorefining applications
Engineered microorganisms convert sugars into valuable platform chemicals that are further derivatized to large-volume chemicals
Priority was assigned based on the projected value of the platform chemical and potential derivatives as well as what technological developments were required for the production of the chemical and associated derivatives [21]
Summary
Organic acids are a valuable sector of the industrial chemical market, which have already been successfully produced through microbial fermentation. Product titers have been variable, ranging from less than 1 g/L to concentrations cost competitive with current petrochemical production processes. These fermentation processes have been limited in E. coli due to product and intermediate toxicity. Toxicity is directly measured by growth inhibition, which decreases productivity. This review highlighted what is known about organic-acid toxicity and tolerance mechanisms in E. coli. E. coli are growth inhibited by the increase in both proton and associated anion concentrations that are characteristic of organic-acid production processes. While several acidtolerance mechanisms have been characterized in E. coli, anion specific mechanisms require additional study. Future metabolic engineering efforts that seek to improve understanding of these issues within the context of organic-acid biorefining applications should prove useful
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