Metabolic engineering of clostridia for the production of chemicals

Abstract

There have recently been signifi cant advances in bio-based production of chemicals from renewable resources. Microorganisms belonging to the genus Clostridium have been considered as one of the promising hosts for the production of desired chemicals of wide industrial use. Clostridium strains have capability to utilize diverse carbon sources, including C5 and C6 substrates, which thus allows production of chemicals from inexpensive and abundant biomass such as corn stover, straw, and woody waste. In addition, Clostridium strains naturally produce various chemicals, such as acetic acid, butyric acid, ethanol, isopropanol, butanol, 1,3-propanediol, 2,3-butanediol, and acetone. Recently, several important strategies for the metabolic engineering of Clostridium have been developed not only for the enhanced production of these natural products and but also for the production of non-natural isobutanol production. Here, we review the strategies employed for the development of metabolically engineered Clostridium strains for the production of such chemicals and provide future perspectives.

Enhanced microbial electrosynthesis by using defined co-cultures

“…Each microorganism can be optimized for its purpose, for example, through genetic engineering, without the need to consider additional tradeoffs imposed by the other process, and there are numerous efforts to engineer homoacetogenic microorganisms to produce, for example, ethanol, butanol and isobutanol (Köpke et al, 2010;Leang et al, 2013;Banerjee et al, 2014;Cho et al, 2015); (2) Only the electron uptaking strain has to contact the cathode while end product formation can proceed in the bulk liquid, which allows better use of the volume of the cathode compartment; (3) two microbial organisms adapt to each other's metabolic capabilities via a thermodynamic-kinetic feedback loop resulting in an optimized metabolic flux without accumulation of intermediates. In addition, mixed communities are often reported to show higher electron transfer rates or higher current efficiencies than pure cultures (Dinh et al, 2004;Nevin et al, 2008;Call et al, 2009;Fast and Papoutsakis, 2012;Ganigue et al, 2015).…”

Efficient gene knockdown in Clostridium acetobutylicum by synthetic small regulatory RNAs

“…C. acetobutylicum is a promising platform strain for the production of important chemicals and biofuels (Cho et al, ; Tracy, ; Tracy et al, ). Recent studies have focused on metabolic engineering of C. acetobutylicum using mobile group II introns to knock out genes of interest in strain development (Jang et al, , ; Lehmann and Lutke‐Eversloh, ).…”

An integrated approach: advances in the use ofClostridiumfor biofuel

“…In the biotechnology sector, progress has been exploited by Tetravitae Biosciences using an extremely stable and robust mutant strain of C. beijerinckii with high selectivity for the butanol production, reduced product inhibition and the ability to effectively use low-cost cellulosic feedstocks (Barnard et al, 2010;Lee, Kweon, Park & Jin, 2009b). A number of reviews on this topic have recently been published, evidencing the renewed interest in this long neglected subject (Cho et al, 2015;Lütke-Eversloh, 2014;Lütke-Eversloh & Bahl, 2011;Shao et al, 2011).…”

“…Due to difficulties in genetic manipulation and complex metabolic regulations, metabolic engineering of Clostridia has been poorly developed and only recently made significant advances (Cho, Jang, Moon, Lee, & Lee, 2015). The regulatory mechanisms controlling solventogenesis began to emerge with the analysis of C. acetobutylicum (Nölling et al, 2001).…”