Systems and Synthetic Biology

Biography

Biography: Reem Swidah

Abstract

Biobutanol represents a second generation   biofuel  , which can be produced naturally by a number of   microorganisms  . This alcohol has a number of significant advantages over bioethanol in terms of its physical properties as a fuel, but production   systems   suffer from various drawbacks. Therefore, we sought to transplant an entire butanol production pathway (the ABE pathway) into a   Saccharomyces cerevisiae   strain. However, this pathway was incapable of generating reasonable yields of butanol without further metabolic alteration to channel carbon towards the substrate of butanol production,   acetyl CoA  . For instance, the major alcohol dehydrogenase, ADH1, was deleted and two enzymes involved in acetyl-CoA   biosynthesis   were overexpressed to give strains capable of producing 300 mg/L butanol. Surprisingly, deletion of the ADH1 gene alone is sufficient to produce 40 mg/L butanol from an endogenous pathway. Previously, this endogenous butanol production pathway was characterized and proposed to derive from the    mitochondrial   catabolism  of threonine via multiple leucine  biosynthetic genes  and the conversion of 2-ketovalerate to butanol. Therefore, in the studies described here, we aimed to understand the relative contribution of exogenous and the endogenous pathways of butanol  synthe sis  to overall butanol yields. Work will be presented to suggest that both pathways are active in yeast  adh1D mutants , but that the endogenous route for butanol synthesis is weaker and does not use the pathway previously proposed via  Leucine  metabolic enzymes . This work therefore makes use of synthetic biology and metabolic engineering to effectively set the scene for an initiative toward s higher yields of butanol in yeast via concerted interventions in both the endogenous and exogenous pathways.