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Weak acids such as acetic acid and formic acid are troublesome inhibitors restricting efficient microbial conversion of the biomass to desired products. To improve our understanding of weak acid inhibition and to identify engineering strategies to reduce acetic acid toxicity, the highly acetic\u2010acid\u2010tolerant yeast <jats:italic>Zygosaccharomyces bailii<\/jats:italic> was studied. The impact of acetic acid membrane permeability on acetic acid tolerance in <jats:italic>Z. bailii<\/jats:italic> was investigated with particular focus on how the previously demonstrated high sphingolipid content in the plasma membrane influences acetic acid tolerance and membrane permeability. Through molecular dynamics simulations, we concluded that membranes with a high content of sphingolipids are thicker and more dense, increasing the free energy barrier for the permeation of acetic acid through the membrane. <jats:italic>Z. bailii<\/jats:italic> cultured with the drug myriocin, known to decrease cellular sphingo\u00adlipid levels, exhibited significant growth inhibition in the presence of acetic acid, while growth in medium without acetic acid was unaffected by the myriocin addition. Furthermore, following an acetic acid pulse, the intracellular pH decreased more in myriocin\u2010treated cells than in control cells. This indicates a higher inflow rate of acetic acid and confirms that the reduction in growth of cells cultured with myriocin in the medium with acetic acid was due to an increase in membrane permeability, thereby demonstrating the importance of a high fraction of sphingolipids in the membrane of <jats:italic>Z. bailii<\/jats:italic> to facilitate acetic acid resistance; a property potentially transferable to desired production organisms suffering from weak acid stress. Biotechnol. Bioeng. 2016;113: 744\u2013753. \u00a9 2015 The Authors. <jats:italic>Biotechnology and Bioengineering<\/jats:italic> Published by Wiley Periodicals, Inc.<\/jats:p><\/jats:sec>","DOI":"10.1002\/bit.25845","type":"journal-article","created":{"date-parts":[[2015,9,29]],"date-time":"2015-09-29T08:25:49Z","timestamp":1443515149000},"page":"744-753","source":"Crossref","is-referenced-by-count":58,"title":["Sphingolipids contribute to acetic acid resistance in <i>Zygosaccharomyces bailii<\/i>"],"prefix":"10.1002","volume":"113","author":[{"given":"Lina","family":"Lindahl","sequence":"first","affiliation":[{"name":"Department of Biology and Biological Engineering Division of Industrial Biotechnology Chalmers University of Technology Gothenburg Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samuel","family":"Genheden","sequence":"additional","affiliation":[{"name":"School of Chemistry University of Southampton Highfield Southampton United Kingdom"},{"name":"Department of Chemistry and Molecular Biology University of Gothenburg Gothenburg Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leif A.","family":"Eriksson","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Molecular Biology University of Gothenburg Gothenburg Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lisbeth","family":"Olsson","sequence":"additional","affiliation":[{"name":"Department of Biology and Biological Engineering Division of Industrial Biotechnology Chalmers University of Technology Gothenburg Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maurizio","family":"Bettiga","sequence":"additional","affiliation":[{"name":"Department of Biology and Biological Engineering Division of Industrial Biotechnology Chalmers University of Technology Gothenburg Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2015,12,10]]},"reference":[{"key":"e_1_2_6_2_1","volume-title":"Computer Simulations of Liquids","author":"Allen M","year":"1987"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1007\/s002030000185"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1021\/j100142a004"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1063\/1.464913"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature08787"},{"key":"e_1_2_6_7_1","unstructured":"Chemical Computing Group Inc.2015. 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