Multi-product microbial cell

Optimization of a Multi-Product Microbial Cell Factory for Multiple Objectives - A Paradigm for Metabolic Pathway Recipe... 

Keywords Multi-product microbial cell factory. Mixed integer MOO (MIMOO), Metabolic pathway recipe, Pareto-optimal set. 

Optimization of a Multi-Product Microbial Cell Factory... 

Almost all works on optimization of a multi-product microbial cell factory focussed on a single objective (e.g., Schmid et al., 2004 Visser et al, 2004 Vital-Lopez et al, 2006). A common feature in these works is the pseudo-stationary assumption. Enzymatic reaction kinetics in a microbial cell factory are reversible and interdependent. In reality, the fluxes due to enzymatic reactions are never stationary. Given the limitations of a model, it is necessary to assume a pseudo-stationary state where some variables fluctuate about an averaged steady state within certain bounds. 

Mihovilovic and coworkers have utilized a microbial Baeyer-Villiger oxidation to desymmetrize readily available 8-oxabicyclo[3.2.1]octene 218. Their key reaction used E. coli in a whole-cell oxidation to give multi-gram quantities of 219 in high optical purity (Scheme 59) [67], To demonstrate its utility they transformed 219 into 220, 221, and 222 thus intercepting intermediates that had previously been converted into the namral products (+)-trani-kumausyne, goniofufurone, and (+)-showdomycin. 

Prior to the widespread awdlabdity of recombiant carbonyl reductases enzymes, the use of microbial reductions using either actively growing or dormant cells was commonplace Bakers yeast in particular, was a readily available source of stereoselective carbonyl reductases enzymes. Even with the widespread knowledge of the power of recombinant CRED biocatalysts, the literature is still rife with wild-type whole-cell microbial reductions. The reductions presented have advanced well beyond the early Bakers yeast reduction and have an apphcation even today. When the whole-cell fermentation is developed and finely tuned, high titers of product alcohol are possible and Scheme 6.4 shows m example of a keto-amide 12 bioreduction performing at 100 g/L with more than 98% ee with multi-kg isolation [12]. The bioprocess was performed over 8 days at pH 7 using the yeast Candida sorbophila. 

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