Microbial production of bi-functional molecules by diversification of the fatty acid pathway

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2016-05
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Garg, Shivani
Rizhsky, Ludmila
Jin, Huanan
Yu, Xiaochen
Jing, Fuyuan
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Copyright © 2016 International Metabolic Engineering Society
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Yandeau-Nelson, Marna
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Nikolau, Basil
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Biochemistry, Biophysics and Molecular BiologyNSF Engineering Research Center for Biorenewable ChemicalsCenter for Metabolic BiologyGenetics, Development and Cell Biology
Abstract
Fatty acids that are chemically functionalized at their ω-ends are rare in nature yet offer unique chemical and physical properties with wide ranging industrial applications as feedstocks for bio-based polymers, lubricants and surfactants. Two enzymatic determinants control this ω-group functionality, the availability of an appropriate acyl-CoA substrate for initiating fatty acid biosynthesis, and a fatty acid synthase (FAS) variant that can accommodate that substrate in the initial condensation reaction of the process. In Type II FAS, 3-ketoacyl-ACP synthase III (KASIII) catalyses this initial condensation reaction. We characterized KASIIIs from diverse bacterial sources, and identified variants with novel substrate specificities towards atypical acyl-CoA substrates, including 3-hydroxybutyryl-CoA. Using Alicyclobacillus acidocaldarius KASIII, we demonstrate the in vivo diversion of FAS to produce novel ω-1 hydroxy-branched fatty acids from glucose in two bioengineered microbial hosts. This study unveils the biocatalytic potential of KASIII for synthesizing diverse ω-functionalized fatty acids.
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This is a manuscript of an article published as Garg, Shivani, Ludmila Rizhsky, Huanan Jin, Xiaochen Yu, Fuyuan Jing, Marna D. Yandeau-Nelson, and Basil J. Nikolau. "Microbial production of bi-functional molecules by diversification of the fatty acid pathway." Metabolic engineering 35 (2016): 9-20. doi:10.1016/j.ymben.2016.01.003. Posted with permission. This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 License.
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