Examining the feasibility of bulk commodity production in Escherichia coli

Abstract

Escherichia coli is currently used by many research institutions and companies around the world as a platform organism for the development of bio-based production processes for bulk biochemicals. A given bulk biochemical bioprocess must be economically competitive with current production routes. Ideally the viability of each bioprocess should be evaluated prior to commencing research, both by metabolic network analysis (to determine the maximum theoretical yield of a given biocatalyst) and by techno-economic analysis (TEA; to determine the conditions required to make the bioprocess cost-competitive). However, these steps are rarely performed. Here we examine theoretical yields and review available TEA for bulk biochemical production in E. coli. In addition, we examine fermentation feedstocks and review recent strain engineering approaches to achieve industrially-relevant production, using examples for which TEA has been performed: ethanol, poly-3-hydroxybutyrate, and 1,3-propanediol.

Can Microbially Derived Advanced Biofuels Ever Compete with Conventional Bioethanol? A Critical Review

“…It should be noted that most E. coli cannot directly utilize sucrose and need to be engineered for sucrose utilization (Sabri et al 2013). Furthermore, if lignocellulosic substrates are used, in addition to exhibiting product tolerance, microbial strains will need to be tolerant to a range of inhibitors while consuming C5 and C6 sugars present in feedstocks (Dien et al 2003;Vickers et al 2012;Ling et al 2014). It is apparent that to be an industrially relevant biofuel producer, the strain will require substantial metabolic engineering and optimization (Yomano et al 1998;Alper and Stephanopoulos 2007;Miller and Ingram 2007;Knoshaug and Zhang 2009).…”

“…Construction of a genetically engineered strain to consume multiple sugars has been shown to compromise product tolerance and yield as well as the ability to tolerate inhibitors (Bellissimi et al 2009;Clomburg and Gonzalez 2010;Vickers et al 2012). Wisselink and coworkers (2009) attempted to evolve the engineered S. cerevisiae on the pentose sugars without losing their performance on hexose sugars.…”

“…However, researchers found that the strain was highly sensitive to inhibitors (Bellisimi et al 2009). Although E. coli is well known for its wide substrate utilization range (it can metabolize both C5 and C6 sugars), genetically engineered E. coli's productivities and yields are not yet high enough for industrial use (Dien et al 2003;Vickers et al 2012). In addition to the recent work on advanced biofuel producing E. coli, research has been carried out for the construction of ethanologenic E. coli, which can consume multiple sugars from lignocellulose (Flores et al 1996;Hernandez-Montalvo et al 2001;Nichols et al 2001;Yomano et al 2009).…”

“…One excellent example is the production of 1,3-propanediol, which is used in a variety of industrial applications including adhesives and coatings. Based on E. coli fermentation, the biochemical process for 1,3-propanediol has proven commercially viable and provides a product quality advantage compared to the petrochemical route (Vickers et al 2012). While the scale of production of isoprenoids or fatty acids for fuel applications would be substantially higher than a "niche" commodity such as 1,3-propanediol, the feasibility of using engineered E. coli for such a large scale production is yet to be proven.…”

Engineering yeast shikimate pathway towards production of aromatics: rational design of a chassis cell using systems and synthetic biology

“…In general, optimization of a fermentation process requires yields, rates and titres to be maximized (Vickers et al, 2012). One possibility to assess the yields of a metabolic network is elementary flux mode (EFM) analysis (EMA) (Schuster & Hilgetag, 1994).…”