caa a22 4500 528785664 20190713030954.0 cr unu---uuuuu 180924s2016 xx s 000 0 eng 10.3929/ethz-b-000114853 doi 10.1038/ncomms11163 doi (ETHRESEARCH)oai:www.research-collection.ethz.ch:20.500.11850/114853 Jeschek Markus Rationally reduced libraries for combinatorial pathway optimization minimizing experimental effort [Elektronische Daten] [Markus Jeschek, Daniel Gerngross, Sven Panke] Nat Commun Open access ethresearch Rational flux design in metabolic engineering approaches remains difficult since important pathway information is frequently not available. Therefore empirical methods are applied that randomly change absolute and relative pathway enzyme levels and subsequently screen for variants with improved performance. However, screening is often limited on the analytical side, generating a strong incentive to construct small but smart libraries. Here we introduce RedLibs (Reduced Libraries), an algorithm that allows for the rational design of smart combinatorial libraries for pathway optimization thereby minimizing the use of experimental resources. We demonstrate the utility of RedLibs for the design of ribosome-binding site libraries by in silico and in vivo screening with fluorescent proteins and perform a simple two-step optimization of the product selectivity in the branched multistep pathway for violacein biosynthesis, indicating a general applicability for the algorithm and the proposed heuristics. We expect that RedLibs will substantially simplify the refactoring of synthetic metabolic pathways. Creative Commons Attribution 4.0 International http://creativecommons.org/licenses/by/4.0 ethresearch Gerngross Daniel joint author Panke Sven joint author Nature Communications London : Nature Publishing Group 7, p. 11163 2041-1723 http://hdl.handle.net/20.500.11850/114853 text/html WWW-Backlink auf das Repository (Open access) 1 Journal Article ethresearch ETHRESEARCH 856 40 http://hdl.handle.net/20.500.11850/114853 text/html WWW-Backlink auf das Repository (Open access) ETHRESEARCH 100 1- Jeschek Markus ETHRESEARCH 700 1- Gerngross Daniel joint author ETHRESEARCH 700 1- Panke Sven joint author ETHRESEARCH 773 0- Nature Communications London : Nature Publishing Group 7, p. 11163 2041-1723 BK010053 XK010053 XK010000 ETHRESEARCH ETHRESEARCH ETHRESEARCH Journal Article Open access