Microbial production of bi-functional molecules by diversification of the fatty acid pathway |
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| Institution: | 1. Graduate Institute of Clinical Medical Science, College of Medicine, China Medical University, Taiwan;2. Division of Nephrology and Kidney Institute, China Medical University Hospital, Taichung, Taiwan;3. Management Office for Health Data, China Medical University Hospital, Taichung, Taiwan;4. College of Medicine, China Medical University, Taichung, Taiwan;5. Division of Pulmonary and Critical Care Medicine, China Medical University Hospital and China Medical University, Taichung, , Taiwan;6. Department of Family Medicine, China Medical University Hospital, Taichung, Taiwan;7. Department of Nuclear Medicine and PET Center, China Medical University Hospital, Taichung, Taiwan |
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| 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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| Keywords: | 3-Ketoacyl-ACP Synthase III Fatty acid synthesis Bio-based chemicals Omega-functionalized fatty acids Substrate diversity Microbial engineering |
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