{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T22:52:55Z","timestamp":1780354375014,"version":"3.54.1"},"reference-count":59,"publisher":"Oxford University Press (OUP)","issue":"17","license":[{"start":{"date-parts":[[2019,1,12]],"date-time":"2019-01-12T00:00:00Z","timestamp":1547251200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100010663","name":"European Research Council","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100010663","id-type":"DOI","asserted-by":"publisher"}]},{"name":"ERC Consolidator","award":["721176"],"award-info":[{"award-number":["721176"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2019,9,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Motivation<\/jats:title>\n                  <jats:p>The computer-aided design of metabolic intervention strategies has become a key component of an integrated metabolic engineering approach and a broad range of methods and algorithms has been developed for this task. Many of these algorithms enforce coupling of growth with product synthesis and may return thousands of possible intervention strategies from which the most suitable strategy must then be selected<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>This work focuses on how to evaluate and rank, in a meaningful way, a given pool of computed metabolic engineering strategies for growth-coupled product synthesis. Apart from straightforward criteria, such as a preferably small number of necessary interventions, a reasonable growth rate and a high product yield, we present several new criteria useful to pick the most suitable intervention strategy. Among others, we investigate the robustness of the intervention strategies by searching for metabolites that may disrupt growth coupling when accumulated or secreted and by checking whether the interventions interrupt pathways at their origin (preferable) or at downstream steps. We also assess thermodynamic properties of the pathway(s) favored by the intervention strategy. Furthermore, strategies that have a significant overlap with alternative solutions are ranked higher because they provide flexibility in implementation. We also introduce the notion of equivalence classes for grouping intervention strategies with identical solution spaces. Our ranking procedure involves in total ten criteria and we demonstrate its applicability by assessing knockout-based intervention strategies computed in a genome-scale model of E.coli for the growth-coupled synthesis of l-methionine and of the heterologous product 1,4-butanediol.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Availability and implementation<\/jats:title>\n                  <jats:p>The MATLAB scripts that were used to characterize and rank the example intervention strategies are available at http:\/\/www2.mpi-magdeburg.mpg.de\/projects\/cna\/etcdownloads.html.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Supplementary information<\/jats:title>\n                  <jats:p>Supplementary data are available at Bioinformatics online.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/bioinformatics\/bty1065","type":"journal-article","created":{"date-parts":[[2019,1,8]],"date-time":"2019-01-08T17:58:56Z","timestamp":1546970336000},"page":"3063-3072","source":"Crossref","is-referenced-by-count":23,"title":["Characterizing and ranking computed metabolic engineering strategies"],"prefix":"10.1093","volume":"35","author":[{"given":"Philipp","family":"Schneider","sequence":"first","affiliation":[{"name":"Max Planck Institute for Dynamics of Complex Technical Systems, Analysis and Redesign of Biological Networks , Magdeburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2563-7561","authenticated-orcid":false,"given":"Steffen","family":"Klamt","sequence":"additional","affiliation":[{"name":"Max Planck Institute for Dynamics of Complex Technical Systems, Analysis and Redesign of Biological Networks , Magdeburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2019,1,12]]},"reference":[{"key":"2023062711320639000_bty1065-B1","author":"Alter","year":"2018"},{"key":"2023062711320639000_bty1065-B2","doi-asserted-by":"crossref","first-page":"148","DOI":"10.1016\/j.ymben.2016.01.009","article-title":"Identification of metabolic engineering targets for the enhancement of 1,4-butanediol production in recombinant E. coli using large-scale kinetic models","volume":"35","author":"Andreozzi","year":"2016","journal-title":"Metab. 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