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By building on multiplex automated genome engineering, we developed a method that enables precise mutagenesis of multiple, long genomic segments in multiple species without off-target modifications. Thereby, it enables the exploration of vast numbers of combinatorial genetic alterations in their native genomic context. This method is especially well-suited to screen the resistance profiles of antibiotic compounds. It allowed us to predict the evolution of resistance against antibiotics currently in clinical trials. 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Gene 84, 143\u2013151 (1989).","journal-title":"Gene"},{"key":"e_1_3_4_32_2","doi-asserted-by":"crossref","first-page":"409","DOI":"10.1016\/B978-0-12-385120-8.00018-8","article-title":"Multiplexed genome engineering and genotyping methods applications for synthetic biology and metabolic engineering","volume":"498","author":"Wang HH","year":"2011","unstructured":"HH Wang, GM Church, Multiplexed genome engineering and genotyping methods applications for synthetic biology and metabolic engineering. 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Biochemistry 32, 3479\u20133487 (1993).","journal-title":"Biochemistry"},{"key":"e_1_3_4_48_2","doi-asserted-by":"crossref","first-page":"11753","DOI":"10.1073\/pnas.90.24.11753","article-title":"Long-range structural effects in a second-site revertant of a mutant dihydrofolate reductase","volume":"90","author":"Brown KA","year":"1993","unstructured":"KA Brown, EE Howell, J Kraut, Long-range structural effects in a second-site revertant of a mutant dihydrofolate reductase. Proc Natl Acad Sci USA 90, 11753\u201311756 (1993).","journal-title":"Proc Natl Acad Sci USA"},{"key":"e_1_3_4_49_2","first-page":"12","article-title":"Mechanisms of action of and resistance to ciprofloxacin","volume":"82","author":"Hooper DC","year":"1987","unstructured":"DC Hooper, JS Wolfson, EY Ng, MN Swartz, Mechanisms of action of and resistance to ciprofloxacin. Am J Med 82, 12\u201320 (1987).","journal-title":"Am J Med"},{"key":"e_1_3_4_50_2","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1111\/nyas.12830","article-title":"Mechanisms of drug resistance: Quinolone resistance","volume":"1354","author":"Hooper DC","year":"2015","unstructured":"DC Hooper, GA Jacoby, Mechanisms of drug resistance: Quinolone resistance. Ann N Y Acad Sci 1354, 12\u201331 (2015).","journal-title":"Ann N Y Acad Sci"},{"key":"e_1_3_4_51_2","doi-asserted-by":"crossref","first-page":"11","DOI":"10.2165\/00003495-199958002-00003","article-title":"Mechanisms of fluoroquinolone resistance: An update 1994-1998","volume":"58","author":"Piddock LJV","year":"1999","unstructured":"LJV Piddock, Mechanisms of fluoroquinolone resistance: An update 1994-1998. Drugs 58, 11\u201318 (1999).","journal-title":"Drugs"},{"key":"e_1_3_4_52_2","doi-asserted-by":"crossref","first-page":"1271","DOI":"10.1128\/AAC.34.6.1271","article-title":"Quinolone resistance-determining region in the DNA gyrase gyrA gene of Escherichia coli","volume":"34","author":"Yoshida H","year":"1990","unstructured":"H Yoshida, M Bogaki, M Nakamura, S Nakamura, Quinolone resistance-determining region in the DNA gyrase gyrA gene of Escherichia coli. Antimicrob Agents Chemother 34, 1271\u20131272 (1990).","journal-title":"Antimicrob Agents Chemother"},{"key":"e_1_3_4_53_2","doi-asserted-by":"crossref","first-page":"11801","DOI":"10.1073\/pnas.92.25.11801","article-title":"Topoisomerase IV is a target of quinolones in Escherichia coli","volume":"92","author":"Khodursky AB","year":"1995","unstructured":"AB Khodursky, EL Zechiedrich, NR Cozzarelli, Topoisomerase IV is a target of quinolones in Escherichia coli. 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Nucleic Acids Res 41, 9911\u20139923 (2013).","journal-title":"Nucleic Acids Res"},{"key":"e_1_3_4_56_2","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1016\/j.ijantimicag.2009.08.003","article-title":"Emergence of a new mutation and its accumulation in the topoisomerase IV gene confers high levels of resistance to fluoroquinolones in Escherichia coli isolates","volume":"35","author":"Moon DC","year":"2010","unstructured":"DC Moon, , Emergence of a new mutation and its accumulation in the topoisomerase IV gene confers high levels of resistance to fluoroquinolones in Escherichia coli isolates. Int J Antimicrob Agents 35, 76\u201379 (2010).","journal-title":"Int J Antimicrob Agents"},{"key":"e_1_3_4_57_2","doi-asserted-by":"crossref","first-page":"1918","DOI":"10.1128\/AAC.02820-15","article-title":"In vitro activity of gepotidacin, a novel triazaacenaphthylene bacterial topoisomerase inhibitor, against a broad spectrum of bacterial pathogens","volume":"60","author":"Biedenbach DJ","year":"2016","unstructured":"DJ Biedenbach, , In vitro activity of gepotidacin, a novel triazaacenaphthylene bacterial topoisomerase inhibitor, against a broad spectrum of bacterial pathogens. Antimicrob Agents Chemother 60, 1918\u20131923 (2016).","journal-title":"Antimicrob Agents Chemother"},{"key":"e_1_3_4_58_2","doi-asserted-by":"crossref","first-page":"e02047-16","DOI":"10.1128\/AAC.02047-16","article-title":"In vitro activity of gepotidacin (GSK2140944) against Neisseria gonorrhoeae","volume":"61","author":"Farrell DJ","year":"2017","unstructured":"DJ Farrell, HS Sader, PR Rhomberg, NE Scangarella-Oman, RK Flamm, In vitro activity of gepotidacin (GSK2140944) against Neisseria gonorrhoeae. Antimicrob Agents Chemother 61, e02047-16 (2017).","journal-title":"Antimicrob Agents Chemother"},{"key":"e_1_3_4_59_2","doi-asserted-by":"crossref","first-page":"1905","DOI":"10.1093\/jac\/dkw061","article-title":"Biological profiling of novel tricyclic inhibitors of bacterial DNA gyrase and topoisomerase IV","volume":"71","author":"Savage VJ","year":"2016","unstructured":"VJ Savage, , Biological profiling of novel tricyclic inhibitors of bacterial DNA gyrase and topoisomerase IV. J Antimicrob Chemother 71, 1905\u20131913 (2016).","journal-title":"J Antimicrob Chemother"},{"key":"e_1_3_4_60_2","doi-asserted-by":"crossref","first-page":"8425","DOI":"10.1038\/ncomms9425","article-title":"Development of potent in vivo mutagenesis plasmids with broad mutational spectra","volume":"6","author":"Badran AH","year":"2015","unstructured":"AH Badran, DR Liu, Development of potent in vivo mutagenesis plasmids with broad mutational spectra. Nat Commun 6, 8425 (2015).","journal-title":"Nat Commun"},{"key":"e_1_3_4_61_2","first-page":"20160151","article-title":"Epistasis between antibiotic resistance mutations and genetic background shape the fitness effect of resistance across species of Pseudomonas","volume":"283","author":"Vogwill T","year":"2016","unstructured":"T Vogwill, M Kojadinovic, RC MacLean, Epistasis between antibiotic resistance mutations and genetic background shape the fitness effect of resistance across species of Pseudomonas. Proc Biol Sci 283, 20160151 (2016).","journal-title":"Proc Biol Sci"},{"key":"e_1_3_4_62_2","doi-asserted-by":"crossref","first-page":"3314","DOI":"10.1093\/molbev\/msu262","article-title":"Testing the role of genetic background in parallel evolution using the comparative experimental evolution of antibiotic resistance","volume":"31","author":"Vogwill T","year":"2014","unstructured":"T Vogwill, M Kojadinovic, V Furi\u00f3, RC MacLean, Testing the role of genetic background in parallel evolution using the comparative experimental evolution of antibiotic resistance. Mol Biol Evol 31, 3314\u20133323 (2014).","journal-title":"Mol Biol Evol"},{"key":"e_1_3_4_63_2","doi-asserted-by":"crossref","first-page":"1626","DOI":"10.1073\/pnas.0709089105","article-title":"Identification and analysis of recombineering functions from Gram-negative and Gram-positive bacteria and their phages","volume":"105","author":"Datta S","year":"2008","unstructured":"S Datta, N Costantino, X Zhou, DL Court, Identification and analysis of recombineering functions from Gram-negative and Gram-positive bacteria and their phages. Proc Natl Acad Sci USA 105, 1626\u20131631 (2008).","journal-title":"Proc Natl Acad Sci USA"},{"key":"e_1_3_4_64_2","doi-asserted-by":"crossref","first-page":"176","DOI":"10.1111\/1751-7915.12846","article-title":"A standardized workflow for surveying recombinases expands bacterial genome-editing capabilities","volume":"11","author":"Ricaurte DE","year":"2018","unstructured":"DE Ricaurte, , A standardized workflow for surveying recombinases expands bacterial genome-editing capabilities. Microb Biotechnol 11, 176\u2013188 (2018).","journal-title":"Microb Biotechnol"},{"key":"e_1_3_4_65_2","doi-asserted-by":"crossref","first-page":"4122","DOI":"10.1073\/pnas.1513315113","article-title":"LNA modification of single-stranded DNA oligonucleotides allows subtle gene modification in mismatch-repair-proficient cells","volume":"113","author":"van Ravesteyn TW","year":"2016","unstructured":"TW van Ravesteyn, , LNA modification of single-stranded DNA oligonucleotides allows subtle gene modification in mismatch-repair-proficient cells. Proc Natl Acad Sci USA 113, 4122\u20134127 (2016).","journal-title":"Proc Natl Acad Sci USA"},{"key":"e_1_3_4_66_2","doi-asserted-by":"crossref","first-page":"527","DOI":"10.1093\/genetics\/163.2.527","article-title":"Targeted nucleotide repair of cyc1 mutations in Saccharomyces cerevisiae directed by modified single-stranded DNA oligonucleotides","volume":"163","author":"Brachman EE","year":"2003","unstructured":"EE Brachman, EB Kmiec, Targeted nucleotide repair of cyc1 mutations in Saccharomyces cerevisiae directed by modified single-stranded DNA oligonucleotides. Genetics 163, 527\u2013538 (2003).","journal-title":"Genetics"},{"key":"e_1_3_4_67_2","doi-asserted-by":"crossref","first-page":"e27","DOI":"10.1093\/nar\/gng027","article-title":"Targeted gene modification in mismatch-repair-deficient embryonic stem cells by single-stranded DNA oligonucleotides","volume":"31","author":"Dekker M","year":"2003","unstructured":"M Dekker, C Brouwers, H te Riele, Targeted gene modification in mismatch-repair-deficient embryonic stem cells by single-stranded DNA oligonucleotides. Nucleic Acids Res 31, e27 (2003).","journal-title":"Nucleic Acids Res"},{"key":"e_1_3_4_68_2","doi-asserted-by":"crossref","first-page":"e147","DOI":"10.1093\/nar\/gkl896","article-title":"Generation of a mouse mutant by oligonucleotide-mediated gene modification in ES cells","volume":"34","author":"Aarts M","year":"2006","unstructured":"M Aarts, M Dekker, S de Vries, A van der Wal, H te Riele, Generation of a mouse mutant by oligonucleotide-mediated gene modification in ES cells. Nucleic Acids Res 34, e147 (2006).","journal-title":"Nucleic Acids Res"},{"key":"e_1_3_4_69_2","doi-asserted-by":"crossref","first-page":"741","DOI":"10.1021\/sb400117c","article-title":"Yeast oligo-mediated genome engineering (YOGE)","volume":"2","author":"DiCarlo JE","year":"2013","unstructured":"JE DiCarlo, , Yeast oligo-mediated genome engineering (YOGE). ACS Synth Biol 2, 741\u2013749 (2013).","journal-title":"ACS Synth Biol"},{"key":"e_1_3_4_70_2","doi-asserted-by":"crossref","first-page":"1453","DOI":"10.1016\/j.cell.2017.10.034","article-title":"Precise editing at DNA replication forks enables multiplex genome engineering in eukaryotes","volume":"171","author":"Barbieri EM","year":"2017","unstructured":"EM Barbieri, P Muir, BO Akhuetie-Oni, CM Yellman, FJ Isaacs, Precise editing at DNA replication forks enables multiplex genome engineering in eukaryotes. Cell 171, 1453\u20131467.e13 (2017).","journal-title":"Cell"},{"key":"e_1_3_4_71_2","doi-asserted-by":"crossref","first-page":"1295","DOI":"10.1038\/nbt.1716","article-title":"Scalable gene synthesis by selective amplification of DNA pools from high-fidelity microchips","volume":"28","author":"Kosuri S","year":"2010","unstructured":"S Kosuri, , Scalable gene synthesis by selective amplification of DNA pools from high-fidelity microchips. Nat Biotechnol 28, 1295\u20131299 (2010).","journal-title":"Nat Biotechnol"},{"key":"e_1_3_4_72_2","doi-asserted-by":"crossref","first-page":"e5629","DOI":"10.1371\/journal.pone.0005629","article-title":"Genetic architecture of intrinsic antibiotic susceptibility","volume":"4","author":"Girgis HS","year":"2009","unstructured":"HS Girgis, AK Hottes, S Tavazoie, Genetic architecture of intrinsic antibiotic susceptibility. PLoS One 4, e5629 (2009).","journal-title":"PLoS One"},{"key":"e_1_3_4_73_2","doi-asserted-by":"crossref","first-page":"422","DOI":"10.1038\/nrmicro.2017.28","article-title":"Next-generation approaches to understand and combat the antibiotic resistome","volume":"15","author":"Crofts TS","year":"2017","unstructured":"TS Crofts, AJ Gasparrini, G Dantas, Next-generation approaches to understand and combat the antibiotic resistome. Nat Rev Microbiol 15, 422\u2013434 (2017).","journal-title":"Nat Rev Microbiol"},{"key":"e_1_3_4_74_2","unstructured":"; The Pew Charitable Trusts Antibiotics Currently in Clinical Development. Available at www.pewtrusts.org\/\u223c\/media\/assets\/2017\/12\/antibiotics_currently_in_clinical_development_09_2017.pdf. Accessed June 8 2017. (2017)."},{"key":"e_1_3_4_75_2","doi-asserted-by":"crossref","first-page":"1521","DOI":"10.1007\/s00253-012-3960-0","article-title":"Pathway redesign for deoxyviolacein biosynthesis in Citrobacter freundii and characterization of this pigment","volume":"94","author":"Jiang PX","year":"2012","unstructured":"PX Jiang, , Pathway redesign for deoxyviolacein biosynthesis in Citrobacter freundii and characterization of this pigment. Appl Microbiol Biotechnol 94, 1521\u20131532 (2012).","journal-title":"Appl Microbiol Biotechnol"},{"key":"e_1_3_4_76_2","doi-asserted-by":"crossref","first-page":"368","DOI":"10.1038\/nrmicro3253","article-title":"Biotechnological domestication of pseudomonads using synthetic biology","volume":"12","author":"Nikel PI","year":"2014","unstructured":"PI Nikel, E Mart\u00ednez-Garc\u00eda, V de Lorenzo, Biotechnological domestication of pseudomonads using synthetic biology. Nat Rev Microbiol 12, 368\u2013379 (2014).","journal-title":"Nat Rev Microbiol"},{"key":"e_1_3_4_77_2","doi-asserted-by":"crossref","first-page":"17803","DOI":"10.1073\/pnas.1409523111","article-title":"Evolution-guided optimization of biosynthetic pathways","volume":"111","author":"Raman S","year":"2014","unstructured":"S Raman, JK Rogers, ND Taylor, GM Church, Evolution-guided optimization of biosynthetic pathways. Proc Natl Acad Sci USA 111, 17803\u201317808 (2014).","journal-title":"Proc Natl Acad Sci USA"},{"key":"e_1_3_4_78_2","doi-asserted-by":"crossref","first-page":"641","DOI":"10.1038\/msb.2012.66","article-title":"Genome-scale engineering for systems and synthetic biology","volume":"9","author":"Esvelt KM","year":"2013","unstructured":"KM Esvelt, HH Wang, Genome-scale engineering for systems and synthetic biology. 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