Emerging engineering principles for yield improvement in microbial cell design

• Main Authors: Santiago Comba, Ana Arabolaza, Hugo Gramajo
• Format: Article
• Language: English
• Published: Elsevier 2012-10-01
• Series: Computational and Structural Biotechnology Journal
• Online Access: http://journals.sfu.ca/rncsb/index.php/csbj/article/view/csbj.201210016

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, selection of appropriate promoter and ribosome binding sites, application of directed evolution of enzymes, and chassis re-circuit. Overall, these approaches tend to be specific for each engineering 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.