Abstract
Carboxylic acids are an attractive biorenewable chemical in terms of their flexibility and usage as precursors for a variety of industrial chemicals. It has been demonstrated that such carboxylic acids can be fermentatively produced using engineered microbes, such as Escherichia coli and Saccharomyces cerevisiae. However, like many other attractive biorenewable fuels and chemicals, carboxylic acids become inhibitory to these microbes at concentrations below the desired yield and titer. In fact, their potency as microbial inhibitors is highlighted by the fact that many of these carboxylic acids are routinely used as food preservatives. This review highlights the current knowledge regarding the impact that saturated, straight-chain carboxylic acids, such as hexanoic, octanoic, decanoic, and lauric acids can have on E. coli and S. cerevisiae, with the goal of identifying metabolic engineering strategies to increase robustness. Key effects of these carboxylic acids include damage to the cell membrane and a decrease of the microbial internal pH. Certain changes in cell membrane properties, such as composition, fluidity, integrity, and hydrophobicity, and intracellular pH are often associated with increased tolerance. The availability of appropriate exporters, such as Pdr12, can also increase tolerance. The effect on metabolic processes, such as maintaining appropriate respiratory function, regulation of Lrp activity and inhibition of production of key metabolites such as methionine, are also considered. Understanding the mechanisms of biocatalyst inhibition by these desirable products can aid in the engineering of robust strains with improved industrial performance.
Highlights
Carboxylic acids are useful biorenewable chemicals that can serve as precursors for drop-in replacements for petroleum-derived industrial chemicals (Mäki-Arvela et al, 2007; Lennen et al, 2010; Shanks, 2010; Carlos Serrano-Ruiz et al, 2012) and biologicallyproduced polymers (Wang et al, 2011) and alcohols (Perez et al, 2013)
Since we are mainly interested in metabolic engineering for carboxylic acid production, we focus on E. coli and S. cerevisiae
Our own studies have shown a significant increase in toxicity to S. cerevisiae on a molar basis as chain length increases from 6 to 8 to 10 carbons (Liu et al, 2013b), but this strong dependence on chain length was not observed with E. coli (Royce et al, 2013)
Summary
Carboxylic acids are useful biorenewable chemicals that can serve as precursors for drop-in replacements for petroleum-derived industrial chemicals (Mäki-Arvela et al, 2007; Lennen et al, 2010; Shanks, 2010; Carlos Serrano-Ruiz et al, 2012) and biologicallyproduced polymers (Wang et al, 2011) and alcohols (Perez et al, 2013). Membrane stress was evidenced by increased permeability of the inner membrane to a nucleic acid dye and an 85% decrease in cell viability associated with carboxylic acid production, where cell viability was quantified by colony forming units relative to the non-producing strain in the same condition (Lennen et al, 2011).
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