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Table 1 Major bottlenecks and possible solutions for ABE fermentation [85]

From: Pathway dissection, regulation, engineering and application: lessons learned from biobutanol production by solventogenic clostridia

Challenges Influences Possible solutions
High feedstock cost Substrates are expensive and compete with nutrition (food versus fuel debate) (i) Construction of novel host or introduction of novel metabolic pathway to utilize cheaper substrates and even carbon dioxide
(ii) Development of physical/chemical pretreatment processes that do not require expensive enzymatic treatment
Low production, yield, and productivity of butanol Increasing feedstock costs, recovery costs, water usage, energy-intensive process, and the cost of effluent treatment (i) Develop strains with improved solvent production and/or develop methods for in situ product removal to alleviate product inhibition
(ii) Develop continuous fermentation processes to increase volumetric productivity
(iii) Develop low-energy methods for solvent recovery and purification
Poor genetic engineering tools Metabolic engineering was inhibited by the low frequencies of transformation and recombination (i) Develop more plasmid vectors and more efficient transformation methods
(ii) Develop more efficient gene knockout methods
Poor understanding of physiology Lack of knowledge of the entire genome and specific genes in the metabolic pathway that could further improve cellular performance (i) Gain a detailed characterization and understanding of acidogenic and solventogenic phases and phase transition
(ii) Systematically develop an understanding of the complex regulatory circuits and their interactions with metabolism 
Bacteriophage contamination (1) Decreasing fermentation rate, (2) change in bacterial cell population and morphology, (3) high levels of unutilized sugars Check through chemical treatment methods, such as: (i) addition of chelating agents to remove divalent cations essential for phage infection, and (ii) use of non-ionic detergents and antibiotics