Genome-scale modeling for metabolic engineering

Abstract

We focus on the application of constraint-based methodologies and, more specifically, flux balance analysis in the field of metabolic engineering, and enumerate recent developments and successes of the field. We also review computational frameworks that have been developed with the express purpose of automatically selecting optimal gene deletions for achieving improved production of a chemical of interest. The application of flux balance analysis methods in rational metabolic engineering requires a metabolic network reconstruction and a corresponding in silico metabolic model for the microorganism in question. For this reason, we additionally present a brief overview of automated reconstruction techniques. Finally, we emphasize the importance of integrating metabolic networks with regulatory information—an area which we expect will become increasingly important for metabolic engineering—and present recent developments in the field of metabolic and regulatory integration.

Genome-Scale, Constraint-Based Modeling of Nitrogen Oxide Fluxes during Coculture of Nitrosomonas europaea and Nitrobacter winogradskyi

“…Genome-scale, constraint-based modeling approaches apply physicochemical, spatiotemporal, and environmental constraints to a reaction network that captures the materials and energy processing activities of a microorganism (28, 29). These models assume that the condition of homeostasis or steady-state operation reached by a microorganism is the result of an optimized physiological response for a given set of environmental conditions (30, 31).…”

Biosynthesis of the Antibiotic Nonribosomal Peptide Penicillin in Baker’s Yeast

“…As engineered heterologous biosynthesis of penicillin has only previously been observed with Hansenula polymorpha, a methylotrophic yeast with large peroxisomes 20 , this suggests that boosting peroxisomal expression further, for example by increasing peroxisome formation, by may be a future approach to improve yields from S. cerevisiae. Further yield improvements could also be achieved using other metabolic engineering strategies 21,22 .…”

BacHBerry: BACterial Hosts for production of Bioactive phenolics from bERRY fruits

“…Recently, several computational methods for in silico metabolic network optimization have emerged and are currently being applied in metabolic engineering (Vera et al 2010;Zomorrodi et al 2012;Machado et al 2015;Simeonidis and Price 2015;Bergdahl et al 2015). They are based on different approaches and rationales, thereby leading to distinct solutions.…”