title: Synthetic biology and regulatory networks: where metabolic systems biology meets control engineering.
abstract: Metabolic pathways can be engineered to maximize the synthesis of various products of interest. With the advent of computational systems biology, this endeavour is usually carried out through in silico theoretical studies with the aim to guide and complement further in vitro and in vivo experimental efforts. Clearly, what counts is the result in vivo, not only in terms of maximal productivity but also robustness against environmental perturbations. Engineering an organism towards an increased production flux, however, often compromises that robustness. In this contribution, we review and investigate how various analytical approaches used in metabolic engineering and synthetic biology are related to concepts developed by systems and control engineering. While trade-offs between production optimality and cellular robustness have already been studied diagnostically and statically, the dynamics also matter. Integration of the dynamic design aspects of control engineering with the more diagnostic aspects of metabolic, hierarchical control and regulation analysis is leading to the new, conceptual and operational framework required for the design of robust and productive dynamic pathways.
authors.affiliation: Department of Automatic Control and Systems Engineering, University of Sheffield, Sheffield S1 3JD, UK.
authors.forename: Fei
authors.initials: F
authors.lastname: He
authors.affiliation: The Manchester Centre for Integrative Systems Biology, Manchester Institute for Biotechnology, School for Chemical Engineering and Analytical Science, University of Manchester, Manchester M1 7DN, UK.
authors.forename: Ettore
authors.initials: E
authors.lastname: Murabito
authors.affiliation: The Manchester Centre for Integrative Systems Biology, Manchester Institute for Biotechnology, School for Chemical Engineering and Analytical Science, University of Manchester, Manchester M1 7DN, UK Department of Synthetic Systems Biology, Swammerdam Institute for Life Sciences, University of Amsterdam, Science Park 904, 1098 XH Amsterdam, The Netherlands Department of Molecular Cell Physiology, VU University Amsterdam, De Boelelaan 1085, 1081 HV Amsterdam, The Netherlands hans.westerhoff@manchester.ac.uk.
authors.forename: Hans V
authors.initials: HV
authors.lastname: Westerhoff
mesh_terms: D060847:Metabolic Engineering / Q000331:legislation & jurisprudence / Q000592:standards / Q000639:trends; D058615:Synthetic Biology / Q000331:legislation & jurisprudence / Q000592:standards / Q000639:trends
keywords: control engineering; gene expression regulation; metabolic engineering; metabolic networks; synthetic biology; systems biology