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. 2020 Jun 19;10:9962. doi: 10.1038/s41598-020-66997-5

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© The Author(s) 2020

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

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Metabolic pathways for 3-alkylphenol production in S. cerevisiae. In S. cerevisiae the heterologous polyketide synthase MSAS, activated by phosphopantetheinyl transferase (NpgA), catalyses the formation of 6-methylsalicylic acid (6-MSA) utilizing malonyl-CoA as extender unit and acetyl-CoA as priming unit. Intracellular propionyl-CoA can be increased by expression of a bacterial propionyl-CoA synthase (PrpE), propionate feeding and deletion of (methyl) citrate synthase genes CIT2/3 to abolish its degradation. MSAS can then utilize propionyl-CoA as priming unit to catalyse the formation of 6-ethylsalicylic acid (6-ESA). The heterologous ‘reverse ß-oxidation’ pathway^21,22 is providing the priming unit butyryl-CoA from acetyl-CoA for the formation of 6-propylsalicylic acid (6-PSA). Finally, 6-MSA decarboxylase (PatG) converts the 6-alkylsalicylic acids, 6-MSA, 6-ESA or 6-PSA, to their respective 3-alkylphenols (3-methylphenol, 3-ethylphenol or 3-propylphenol) that are valuable tsetse fly attractants.