title: Complex systems in metabolic engineering.
abstract: Metabolic engineers manipulate intricate biological networks to build efficient biological machines. The inherent complexity of this task, derived from the extensive and often unknown interconnectivity between and within these networks, often prevents researchers from achieving desired performance. Other fields have developed methods to tackle the issue of complexity for their unique subset of engineering problems, but to date, there has not been extensive and comprehensive examination of how metabolic engineers use existing tools to ameliorate this effect on their own research projects. In this review, we examine how complexity affects engineering at the protein, pathway, and genome levels within an organism, and the tools for handling these issues to achieve high-performing strain designs. Quantitative complexity metrics and their applications to metabolic engineering versus traditional engineering fields are also discussed. We conclude by predicting how metabolic engineering practices may advance in light of an explicit consideration of design complexity.
authors: Department of Chemical and Biological Engineering, University of Colorado-Boulder, Jennie Smoly Caruthers Biotechnology Building, Research Park, Boulder, CO 80303, USA.
authors: James D
authors: JD
authors: Winkler
authors: Department of Chemical and Biological Engineering, University of Colorado-Boulder, Jennie Smoly Caruthers Biotechnology Building, Research Park, Boulder, CO 80303, USA.
authors: Keesha
authors: K
authors: Erickson
authors: Department of Chemical and Biological Engineering, University of Colorado-Boulder, Jennie Smoly Caruthers Biotechnology Building, Research Park, Boulder, CO 80303, USA.
authors: Alaksh
authors: A
authors: Choudhury
authors: Department of Chemical and Biological Engineering, University of Colorado-Boulder, Jennie Smoly Caruthers Biotechnology Building, Research Park, Boulder, CO 80303, USA.
authors: Andrea L
authors: AL
authors: Halweg-Edwards
authors: Department of Chemical and Biological Engineering, University of Colorado-Boulder, Jennie Smoly Caruthers Biotechnology Building, Research Park, Boulder, CO 80303, USA. Electronic address: rtg@colorado.edu.
authors: Ryan T
authors: RT
authors: Gill
mesh_terms: D016678:Genome; D006801:Humans; D060847:Metabolic Engineering / Q000379:methods*; D053858:Metabolic Networks and Pathways; D011506:Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: D011506:Proteins