(641d) Omics Guided Rationally Metabolic Engineering of Clostridium Tyrobutyricum

The objective of this study was to achieve high butanol production by rational metabolic engineering of Clostridium tyrobutyricum. Our proteomics analysis showed that the expression of thiolase (thl) that converts acetyl-CoA to acetoacetyl-CoA and the butanol dehydrogenase (bdh) that catalyzes the formation of butanol from butyryldehyde had strong correlation with butanol production. These enzymes regulated carbon metabolism or/and redox balance in the metabolic pathway of butanol production. Then the homogenous thl gene and heterologous bdh gene from C. acetobutylicum were overexpressed in butanol producing mutant of C. tyrobutyricum. Both single- and double-vector gene expression systems with optimized promoter were developed to rationally engineer C. tyrobutyricum. The butanol fermentation showed that the redirection of carbon in the central metabolic pathway greatly improved the butanol titer to > 20 g/L and selectivity > 0.90 g/g. This study revealed that the Omics guided metabolic engineering is an efficient cell engineering strategy to achieve high biobutanol production.