title: Microbial production of bi-functional molecules by diversification of the fatty acid pathway.
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.
authors.affiliation: Department of Biochemistry, Biophysics and Molecular Biology, Iowa State University, Ames, IA, USA; NSF Engineering Research Center for Biorenewable Chemicals, Iowa State University, Ames, IA, USA. Electronic address: garg@iastate.edu.
authors.forename: Shivani
authors.initials: S
authors.lastname: Garg
authors.affiliation: Department of Biochemistry, Biophysics and Molecular Biology, Iowa State University, Ames, IA, USA; OmegaChea Biorenewables LLC, Ames, IA, USA. Electronic address: ludmilar@iastate.edu.
authors.forename: Ludmila
authors.initials: L
authors.lastname: Rizhsky
authors.affiliation: Department of Biochemistry, Biophysics and Molecular Biology, Iowa State University, Ames, IA, USA; NSF Engineering Research Center for Biorenewable Chemicals, Iowa State University, Ames, IA, USA; Center for Metabolic Biology, Iowa State University, Ames, IA, USA. Electronic address: huananjin@mail.hzau.edu.cn.
authors.forename: Huanan
authors.initials: H
authors.lastname: Jin
authors.affiliation: Department of Biochemistry, Biophysics and Molecular Biology, Iowa State University, Ames, IA, USA; NSF Engineering Research Center for Biorenewable Chemicals, Iowa State University, Ames, IA, USA; Center for Metabolic Biology, Iowa State University, Ames, IA, USA. Electronic address: yux@iastate.edu.
authors.forename: Xiaochen
authors.initials: X
authors.lastname: Yu
authors.affiliation: Department of Biochemistry, Biophysics and Molecular Biology, Iowa State University, Ames, IA, USA; NSF Engineering Research Center for Biorenewable Chemicals, Iowa State University, Ames, IA, USA. Electronic address: fyjing@iastate.edu.
authors.forename: Fuyuan
authors.initials: F
authors.lastname: Jing
authors.affiliation: NSF Engineering Research Center for Biorenewable Chemicals, Iowa State University, Ames, IA, USA; Department of Genetics, Development and Cell Biology, Iowa State University, Ames, IA, USA. Electronic address: myn@iastate.edu.
authors.forename: Marna D
authors.initials: MD
authors.lastname: Yandeau-Nelson
authors.affiliation: Department of Biochemistry, Biophysics and Molecular Biology, Iowa State University, Ames, IA, USA; NSF Engineering Research Center for Biorenewable Chemicals, Iowa State University, Ames, IA, USA; Center for Metabolic Biology, Iowa State University, Ames, IA, USA. Electronic address: dimmas@iastate.edu.
authors.forename: Basil J
authors.initials: BJ
authors.lastname: Nikolau
mesh_terms: D001419:Bacteria / Q000201:enzymology / Q000235:genetics; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism; D064429:Fatty Acid Synthases / Q000235:genetics / Q000378:metabolism; D005227:Fatty Acids / Q000096:biosynthesis / Q000235:genetics
chemical_list: D001426:Bacterial Proteins; D005227:Fatty Acids; D064429:Fatty Acid Synthases
keywords: 3-Ketoacyl-ACP Synthase III; Bio-based chemicals; Fatty acid synthesis; Microbial engineering; Omega-functionalized fatty acids; Substrate diversity