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Metab Eng. 2016 May;35:9-20. doi: 10.1016/j.ymben.2016.01.003. Epub 2016 Jan 28.

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

Author information

1
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.
2
Department of Biochemistry, Biophysics and Molecular Biology, Iowa State University, Ames, IA, USA; OmegaChea Biorenewables LLC, Ames, IA, USA. Electronic address: ludmilar@iastate.edu.
3
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.
4
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.
5
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.
6
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.
7
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.

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.

KEYWORDS:

3-Ketoacyl-ACP Synthase III; Bio-based chemicals; Fatty acid synthesis; Microbial engineering; Omega-functionalized fatty acids; Substrate diversity

PMID:
26827988
DOI:
10.1016/j.ymben.2016.01.003
[Indexed for MEDLINE]

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