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Although researchers have published many studies on the design of metabolic systems based on kinetic models and optimization strategies, almost no studies discuss the multi-objective optimization problem for enzyme manipulations in metabolic networks considering resilience phenomenon.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results<\/jats:title>\n            <jats:p>This study proposes a generalized fuzzy multi-objective optimization approach to formulate the enzyme intervention problem for metabolic networks considering resilience phenomena and cell viability. This approach is a general framework that can be applied to any metabolic networks to investigate the influence of resilience phenomena on gene intervention strategies and maximum target synthesis rates. This study evaluates the performance of the proposed approach by applying it to two metabolic systems: <jats:italic>S. cerevisiae<\/jats:italic> and <jats:italic>E. coli<\/jats:italic>. Results show that the maximum synthesis rates of target products by genetic interventions are always over-estimated in metabolic networks that do not consider the resilience effects.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p>Considering the resilience phenomena in metabolic networks can improve the predictions of gene intervention and maximum synthesis rates in metabolic engineering. The proposed generalized fuzzy multi-objective optimization approach has the potential to be a good and practical framework in the design of metabolic networks.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1186\/1752-0509-5-145","type":"journal-article","created":{"date-parts":[[2011,9,20]],"date-time":"2011-09-20T08:47:44Z","timestamp":1316508464000},"update-policy":"http:\/\/dx.doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Multi-objective optimization of enzyme manipulations in metabolic networks considering resilience effects"],"prefix":"10.1186","volume":"5","author":[{"given":"Wu-Hsiung","family":"Wu","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Feng-Sheng","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maw-Shang","family":"Chang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2011,9,19]]},"reference":[{"key":"752_CR1","doi-asserted-by":"publisher","first-page":"82","DOI":"10.1002\/1097-0290(20001005)70:1<82::AID-BIT10>3.0.CO;2-V","volume":"70","author":"F Alvarez-Vasquez","year":"2000","unstructured":"Alvarez-Vasquez F, Gonz\u00e1lez-Alc\u00f3n C, Torres NV: Metabolism of citric acid production by Aspergillus niger: Model definition, steady-state analysis and constrained optimization of citric acid production rate. 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