کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
31877 44847 2010 17 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Modeling and optimization of a multi-product biosynthesis factory for multiple objectives
موضوعات مرتبط
مهندسی و علوم پایه مهندسی شیمی بیو مهندسی (مهندسی زیستی)
پیش نمایش صفحه اول مقاله
Modeling and optimization of a multi-product biosynthesis factory for multiple objectives
چکیده انگلیسی

Genetic algorithms and optimization in general, enable us to probe deeper into the metabolic pathway recipe for multi-product biosynthesis. An augmented model for optimizing serine and tryptophan flux ratios simultaneously in Escherichia coli, was developed by linking the dynamic tryptophan operon model and aromatic amino acid-tryptophan biosynthesis pathways to the central carbon metabolism model. Six new kinetic parameters of the augmented model were estimated with considerations of available experimental data and other published works. Major differences between calculated and reference concentrations and fluxes were explained. Sensitivities and underlying competition among fluxes for carbon sources were consistent with intuitive expectations based on metabolic network and previous results. Biosynthesis rates of serine and tryptophan were simultaneously maximized using the augmented model via concurrent gene knockout and manipulation. The optimization results were obtained using the elitist non-dominant sorting genetic algorithm (NSGA-II) supported by pattern recognition heuristics. A range of Pareto-optimal enzyme activities regulating the amino acids biosynthesis was successfully obtained and elucidated wherever possible vis-à-vis fermentation work based on recombinant DNA technology. The predicted potential improvements in various metabolic pathway recipes using the multi-objective optimization strategy were highlighted and discussed in detail.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Metabolic Engineering - Volume 12, Issue 3, May 2010, Pages 251–267
نویسندگان
, , ,