Emerging engineering principles for yield improvement in microbial cell design

SANTIAGO COMBA, ANA ARABOLAZA (CORRESPONDING) AND HUGO GRAMAJO

Computational and Structural Biotechnology Journal

Research Network of Computational and Structural Biotechnology (RNCSB)

Año: 2012 vol. 3 p. 1 - 6

2001-0370

Metabolic Engineering has undertaken a rapid transformation in the last ten years making real progress towards the production of a wide range of molecules and fine chemicals using a designed cellular host. However, the maximization of product yields through pathway optimization is a constant and central challenge of this field. Traditional methods used to improve the production of target compounds from engineered biosynthetic pathways in non-native hosts include: codon usage optimization, elimination of the accumulation of toxic intermediates or byproducts, enhanced production of rate-limiting enzymes, selectionof appropriate promoter and ribosome binding sites, application of directed evolution ofenzymes, and chassis re-circuit. Overall, these approaches tend to be specific for eachengineering project rather than a systematic practice based on a more generalizable strategy. In this mini-review, we highlight some novel and extensive approaches and tools intended to address the improvement of a target product formation, founded in sophisticated principles such as dynamic control, pathway genes modularization, and flux modeling.