High butanol production by regulating carbon, redox and energy in Clostridia

Improving Fructose Utilization and Butanol Production by Clostridium acetobutylicum via Extracellular Redox Potential Regulation and Intracellular Metabolite Analysis

“…[39] It was reported that ATP could play a major role not only increasing ABE production but also regulating the metabolic shift towards solventogenesis. [26] Grupe and Gottschalk showed that low ATP level resulted in acids formation, but high ATP level responded to ABE biosynthesis in continuous fermentation. [40] Moreover, high ATP level could generate a driving force for the reaction of acetyl-CoA to acetoacetyl-CoA while inhibit the butyrate-producing pathway, [41][42][43] leading to more carbon flux redistributed toward butanol production.…”

“…For example, increasing hydrogen partial pressure, sparging carbon monoxide, and using exogenous additives such as artificial electron carriers, biological redox pairs, and co-substrate could contribute to butanol biosynthesis, butanol yield, and butanol/acetone ratio by affecting not only extracellular ORP levels but also intracellular NADH availability or NADH/NAD þ ratio. [26,27,30] As for C. acetobutylicum, its hydrogenase activity is inhibited by glycerol or some artificial electron carriers, leading to weak hydrogen production and electron flow redistributed towards butanol as the major source for NADH consumption. Consequently, increasing ATP and NADH availabilities has been proposed as efficient genetic and bioprocess engineering manipulations to improve clostridial traits by inducing metabolic perturbations for redistributing carbon flux and enhancing butanol production.…”

“…Consequently, increasing ATP and NADH availabilities has been proposed as efficient genetic and bioprocess engineering manipulations to improve clostridial traits by inducing metabolic perturbations for redistributing carbon flux and enhancing butanol production. [26,27,44] In this study, the ORP control was validated as an effective bioprocess engineering strategy, which might be applied for improving ABE fermentation by C. acetobutylicum. The extracellular ORP-mediated effect on ABE fermentation from the mixture of fructose and glucose to simulate the hydrolysate of JA tubers was evaluated with ORP control strategies, and the experimental results showed that the extracellular ORP controlled above À460 mV played a crucial role in enhancing fructose utilization, metabolic shift toward solventogenesis, and butanol biosynthesis.…”

“…[23,24] However, ABE fermentation by C. acetobutylicum inherently depends on successful transition from acidogenesis to solventogenesis, which has been proven to be triggered by both extracellular and intracellular cues such as the accumulation of undissociated acids, environmental pH, levels of intermediate metabolites, and cofactors as well as the regulation of gene expression by transcriptional factors, [25] implying a coordination of biophysical, metabolic and regulatory responses resulting from intracellular interreactions to culture conditions. Among these multiple variables, extracellular redox potential or oxidation-reduction potential (ORP) has been extensively investigated as a major regulatory factor involved in manipulating biphasic metabolism via bioprocess engineering approaches such as sparging reductive gases and supplementing exogenous additives, [26,27] provoking an in-depth exploration for mechanism underlying metabolic shift toward solventogenesis in C. acetobutylicum. Therefore, the objective of this work is to evaluate the regulation of extracellular ORP on fructose utilization, butanol biosynthesis, and metabolic shift toward solventogenesis in C. acetobutylicum using a mixture of fructose and glucose to simulate the hydrolysate of JA tubers.…”

Genetic engineering of non-native hosts for 1-butanol production and its challenges: a review

“…The advances and challenges in the engineering of 1-butanol production strains using clostridial species, which are the native 1-butanol producers, have been extensively discussed [8,16,[33][34][35]. However, a comprehensive review on the engineering of non-native hosts for 1-butanol production is still absent.…”