title: Engineering Saccharomyces cerevisiae to produce odd chain-length fatty alcohols.
abstract: Fatty aldehydes and alcohols are valuable precursors used in the industrial manufacturing of a myriad of specialty products. Herein, we demonstrate the de novo production of odd chain-length fatty aldehydes and fatty alcohols in Saccharomyces cerevisiae by expressing a novel biosynthetic pathway involving cytosolic thioesterase, rice α-dioxygenase and endogenous aldehyde reductases. We attained production titers of ∼20 mg/l fatty aldehydes and ∼20 mg/l fatty alcohols in shake flask cultures after 48 and 60 h respectively without extensive fine-tuning of metabolic fluxes. In contrast to prior studies which relied on bi-functional fatty acyl-CoA reductase to produce even chain-length fatty alcohols, our biosynthetic route exploits α-oxidation reaction to produce odd chain-length fatty aldehyde intermediates without using NAD(P)H cofactor, thereby conserving cellular resource during the overall synthesis of odd chain-length fatty alcohols. The biosynthetic pathway presented in this study has the potential to enable sustainable and efficient synthesis of fatty acid-derived chemicals from processed biomass.
authors.affiliation: Key Laboratory of Systems Bioengineering (Ministry of Education), Tianjin University, Tianjin, 300072, PR China.|SynBio Research Platform, Collaborative Innovation Center of Chemical Science and Engineering, School of Chemical Engineering and Technology, Tianjin University, Tianjin, 300072, PR China.|Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, 14 Medical Drive, 117599, Singapore.|NUS Synthetic Biology for Clinical and Technological Innovation (SynCTI), Life Sciences Institute, National University of Singapore, 28 Medical Drive, 117456, Singapore.
authors.forename: Zhu
authors.initials: Z
authors.lastname: Jin
authors.affiliation: Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, 14 Medical Drive, 117599, Singapore.|NUS Synthetic Biology for Clinical and Technological Innovation (SynCTI), Life Sciences Institute, National University of Singapore, 28 Medical Drive, 117456, Singapore.
authors.forename: Adison
authors.initials: A
authors.lastname: Wong
authors.affiliation: Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, 14 Medical Drive, 117599, Singapore.|NUS Synthetic Biology for Clinical and Technological Innovation (SynCTI), Life Sciences Institute, National University of Singapore, 28 Medical Drive, 117456, Singapore.
authors.forename: Jee Loon
authors.initials: JL
authors.lastname: Foo
authors.affiliation: Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, 14 Medical Drive, 117599, Singapore.|NUS Synthetic Biology for Clinical and Technological Innovation (SynCTI), Life Sciences Institute, National University of Singapore, 28 Medical Drive, 117456, Singapore.
authors.forename: Joey
authors.initials: J
authors.lastname: Ng
authors.affiliation: Key Laboratory of Systems Bioengineering (Ministry of Education), Tianjin University, Tianjin, 300072, PR China.|SynBio Research Platform, Collaborative Innovation Center of Chemical Science and Engineering, School of Chemical Engineering and Technology, Tianjin University, Tianjin, 300072, PR China.
authors.forename: Ying-Xiu
authors.initials: YX
authors.lastname: Cao
authors.affiliation: Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, 14 Medical Drive, 117599, Singapore. bchcmw@nus.edu.sg.|NUS Synthetic Biology for Clinical and Technological Innovation (SynCTI), Life Sciences Institute, National University of Singapore, 28 Medical Drive, 117456, Singapore. bchcmw@nus.edu.sg.
authors.forename: Matthew Wook
authors.initials: MW
authors.lastname: Chang
authors.affiliation: Key Laboratory of Systems Bioengineering (Ministry of Education), Tianjin University, Tianjin, 300072, PR China. yjyuan@tju.edu.cn.|SynBio Research Platform, Collaborative Innovation Center of Chemical Science and Engineering, School of Chemical Engineering and Technology, Tianjin University, Tianjin, 300072, PR China. yjyuan@tju.edu.cn.
authors.forename: Ying-Jin
authors.initials: YJ
authors.lastname: Yuan
mesh_terms: D000447:Aldehydes / Q000378:metabolism; D053898:Biosynthetic Pathways / Q000235:genetics*; D005227:Fatty Acids / Q000378:metabolism; D005233:Fatty Alcohols / Q000378:metabolism*; D015870:Gene Expression; D060847:Metabolic Engineering / Q000379:methods*; D012275:Oryza; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000235:genetics* / Q000378:metabolism*
chemical_list: D000447:Aldehydes; D005227:Fatty Acids; D005233:Fatty Alcohols; D011994:Recombinant Proteins; C001634:fatty aldehyde
keywords: fatty alcohols; fatty aldehydes; metabolic engineering; saccharomyces cerevisiae