Submitted to: Global Biofuels & Bioproducts Summit (OMICS Group Conferences)
Publication Type: Abstract Only
Publication Acceptance Date: 8/20/2012
Publication Date: 11/20/2012
Citation: Flythe, M.D. 2012. Metabolic control of Clostridium thermocellum via selective inhibition and compensatory product formation. Global Biofuels & Bioproducts Summit (OMICS Group Conferences). 3:7.
Technical Abstract: Clostridium thermocellum is a thermophilic, anaerobic bacterium that catabolizes recalcitrant plant fibers such as cellulose. Cellulose is depolymerized by an extracellular, membrane-associated enzyme system, and the sugars are then transported across the cell membrane for fermentation. C. thermocellum produces ethanol, but only as part of a mixed-acid fermentation. Acetate is the major product under optimal growth conditions, and cellular reducing equivalents (e.g. NAD+) are regenerated via hydrogenase enzymes, which produce H2. However, reducing equivalents can also be recovered with dehydrogenase enzymes, such as lactate dehydrogenase and acetaldehyde/ethanol dehydrogenase. The ethanol yield was improved by as much as 350% when H2 production was selectively inhibited with hydrogenase inhibitors, exogenous H2, or elevated hyperbaric pressure. However, these gains were only realized when lactate production was controlled by limiting the rate of substrate (sugar) transport. Substrate limitation was achieved in a chemostat or by inhibition of sugar transport across the cell membrane. Fortuitously, the hydrogenase inhibitor methyl viologen (paraquat) also inhibited sugar transport by C. thermocellum, and stimulated ethanol production. The concept of driving compensatory product formation via selective inhibition of metabolic pathways is broadly applicable to microorganisms that make more than one product. In particular, the clostridia (including those that produce other solvents) are amenable to selective inhibition because of the sensitivity of their hydrogenases.