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Solutions to improve product yields or alleviate such toxicity using the techniques of modern molecular biology first require a detailed understanding of the mechanisms of product toxicity. Here we have studied the economically important flavor compound vanillin, an aromatic aldehyde that exerts significant toxic effects on bacterial cells. We used high-resolution protein abundance analysis as a starting point to determine which proteins are upregulated and which are downregulated by growth with vanillin, followed by gene expression and mutant studies to understand the mechanism of the response. In a second approach, we evolved bacterial strains with higher vanillin tolerance. Their genome sequences have yielded novel insights into vanillin tolerance that are complementary to the proteomics data set.<\/jats:p>","DOI":"10.1128\/msystems.00163-19","type":"journal-article","created":{"date-parts":[[2019,6,10]],"date-time":"2019-06-10T14:21:07Z","timestamp":1560176467000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":47,"title":["Proteomic Profiling, Transcription Factor Modeling, and Genomics of Evolved Tolerant Strains Elucidate Mechanisms of Vanillin Toxicity in Escherichia coli"],"prefix":"10.1128","volume":"4","author":[{"given":"Calum A.","family":"Pattrick","sequence":"first","affiliation":[{"name":"Department of Molecular Biology and Biotechnology, The University of Sheffield, Sheffield, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2825-7671","authenticated-orcid":false,"given":"Joseph 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